{"id":6432,"date":"2025-09-18T19:37:25","date_gmt":"2025-09-18T19:37:25","guid":{"rendered":"https:\/\/polikistikover.net\/yeni\/?page_id=6432"},"modified":"2025-11-15T22:31:42","modified_gmt":"2025-11-15T22:31:42","slug":"polikistik-over-sendromunda-adet-duzensizligi-ve-tedavisi","status":"publish","type":"page","link":"https:\/\/polikistikover.net\/yeni\/polikistik-over-sendromunda-adet-duzensizligi-ve-tedavisi\/","title":{"rendered":"Polikistik Over Sendromu\u2019nda Adet D\u00fczensizli\u011fi ve Tedavisi"},"content":{"rendered":"\n


Bir adet kanamas\u0131n\u0131n ba\u015flang\u0131c\u0131ndan itibaren takip<\/mark> eden adet kanamas\u0131n\u0131n ilk g\u00fcn\u00fcne kadar ge\u00e7en s\u00fcre bir adet d\u00f6ng\u00fcs\u00fcd\u00fcr (menstrual cycle).<\/mark><\/strong><\/p>\n\n\n\n

Polikistik over sendromu olan kad\u0131nlar\u0131n b\u00fcy\u00fck bir k\u0131sm\u0131n\u0131n adet d\u00f6ng\u00fclerinde d\u00fczensizlik vard\u0131r(1,4,5,7,8,9). <\/mark><\/strong><\/p>\n\n\n\n

Polikistik over sendromu\u2019nda adet d\u00fczensizli\u011fi de\u011fi\u015fik \u015fekillerde ortaya \u00e7\u0131kmaktad\u0131r<\/mark><\/strong>;<\/p>\n\n\n\n

1-<\/mark><\/strong> Bu kad\u0131nlarda \u00e7o\u011funlukla 35 g\u00fcn ile 3 ay aras\u0131nda de\u011fi\u015fen aral\u0131klarla (oligomenorrhea) adet kanamalar\u0131 (2,4,7,8,9). <\/p>\n\n\n\n

2-<\/mark><\/strong> Daha k\u00fc\u00e7\u00fck bir k\u0131sm\u0131nda ise 3 aydan daha uzun aral\u0131klarla (amenorrhea) adet kanamalar\u0131 g\u00f6r\u00fclmektedir(2,5,7,8,,9).<\/p>\n\n\n\n

3-<\/mark><\/strong> Polikistik over senmu olan kad\u0131nlar\u0131n bir b\u00f6l\u00fcm\u00fcnde ise adet d\u00fczensizli\u011fi yoktur. Adet d\u00fczensizli\u011fi olmayanlarda adet kanamalar\u0131 21 ila 35 g\u00fcnde bir (eumenorrhea) olmaktad\u0131r(2,3,6,9).<\/p>\n\n\n\n

4-<\/mark><\/strong> Lekelenme \u015feklinde az miktarda veya fazla miktarda, koyu renkli, p\u0131ht\u0131l\u0131 uzun s\u00fcre devam eden adet kanamalar\u0131 (menometrorrhagia)  polikistik over sendromu olan kad\u0131nlar\u0131n bir k\u0131sm\u0131nda ortaya \u00e7\u0131kmaktad\u0131r(1,2,5,7,8,9). <\/p>\n\n\n\n

5-<\/mark><\/strong> Bu kad\u0131nlar\u0131n bir b\u00f6l\u00fcm\u00fcnde adet kanamalar\u0131n\u0131n 21 g\u00fcnden daha s\u0131k aral\u0131klarla oldu\u011fu (polymenorrhea) da g\u00f6r\u00fclmektedir (1,5,7,8,9).<\/p>\n\n\n\n

Polikistik over sendromu olan kad\u0131nlar\u0131n bir k\u0131sm\u0131nda 35 ila 90 g\u00fcnde bir g\u00f6r\u00fclen bir ka\u00e7 adet kanamas\u0131n\u0131 21 ila 35 g\u00fcnde bir g\u00f6r\u00fclen d\u00fczenli adet kanamalar\u0131 takip etmekte ve bir s\u00fcre sonra ayn\u0131 kad\u0131nda adet kanamalar\u0131 tekrar 35 ila 90 g\u00fcnde bir g\u00f6r\u00fclmeye devam etmektedir(6,25).<\/mark><\/strong><\/p>\n\n\n

\n
\"\"<\/figure>\n<\/div>\n\n\n

1-<\/mark><\/strong> Gebeli\u011fin 20. haftas\u0131nda fetus yumurtal\u0131klar\u0131nda yakla\u015f\u0131k 7 milyon \u00fcreme h\u00fccresi (oocyte) vard\u0131r(14,15,16,19).<\/p>\n\n\n\n

2-<\/mark><\/strong> H\u0131zl\u0131 bir \u015fekilde \u00f6ld\u00fckleri (atresia) (apoptosis) i\u00e7in do\u011fumda yakla\u015f\u0131k 1 milyon \u00fcreme h\u00fccresi kalmaktad\u0131r(14,15,16,17,19).<\/p>\n\n\n\n

3- <\/mark><\/strong>Ergenlik d\u00f6neminin ba\u015f\u0131nda \u00fcreme h\u00fccresi say\u0131s\u0131 400 bin civar\u0131na inmektedir.<\/p>\n\n\n\n

4-<\/mark><\/strong> Ergenlik d\u00f6neminden itibaren menopoz d\u00f6nemine kadar her adet d\u00f6ng\u00fcs\u00fcnde (menstrual cycle) yumurtlama (ovulation) i\u00e7in bir yumurta kullan\u0131lmaktad\u0131r(14,15,18).<\/p>\n\n\n\n

 Ergenlik d\u00f6neminden itibaren menopoz d\u00f6nemine kadar yumurtlaman\u0131n oldu\u011fu adet d\u00f6ng\u00fclerinin (menstrual cycle) toplam\u0131nda yakla\u015f\u0131k 400 tane yumurta kullan\u0131lmaktad\u0131r(14,15,18,19,20).<\/mark><\/strong><\/p>\n\n\n\n

Bir yumurtlaman\u0131n oldu\u011fu her adet d\u00f6ng\u00fcs\u00fcnde 1000 tane yumurta da \u00f6lmektedir (atresia) (apoptosis)(14,15,18,19,20).<\/mark><\/strong> <\/p>\n\n\n\n

Bunun sonucunda menopoz \u00f6ncesi d\u00f6nemde yumurta say\u0131s\u0131 1000 civar\u0131na kadar inmekte ve bir s\u00fcre sonra menopoz d\u00f6neminde de bitmektedir(14,15,18,19).<\/mark><\/strong><\/p>\n\n\n

\n
\"\"<\/figure>\n<\/div>\n\n\n

Bir adet d\u00f6ng\u00fcs\u00fcnde (menstrual cycle) \u00fcreme h\u00fccresini (oosit) i\u00e7inde ta\u015f\u0131yan k\u00fc\u00e7\u00fck folik\u00fcllerden (antral) (5-10 mm) bir tanesi se\u00e7ildikten sonra yumurtlama \u00f6ncesi olgun folik\u00fcl (dominant) (20 mm) halini almaktad\u0131r(10,11,12,13,35,37). Yumurtlama (ovulasyon) bu folik\u00fcl i\u00e7inden \u00fcreme h\u00fccresinin (oosit) d\u0131\u015far\u0131ya \u00e7\u0131kmas\u0131yla olu\u015fmaktad\u0131r(10,11,12,13).<\/mark><\/strong><\/p>\n\n\n\n

1-<\/mark><\/strong>Polikistik over sendromu olan kad\u0131nlarda \u00fcreme h\u00fccrelerini (oocyte) i\u00e7inde ta\u015f\u0131yan dinlenme a\u015famas\u0131nda bulunan en k\u00fc\u00e7\u00fck folik\u00fcllerde (resting follicles) (primordial folik\u00fcl) h\u0131zl\u0131 bir b\u00fcy\u00fcme g\u00f6r\u00fclmektedir(21,22). H\u0131zl\u0131 b\u00fcy\u00fcyen bu k\u00fc\u00e7\u00fck folik\u00fcllerin \u00f6l\u00fcm (atresia) (apoptosis) oranlar\u0131 da d\u00fc\u015f\u00fck olup canl\u0131l\u0131klar\u0131n\u0131 (survival) s\u00fcrd\u00fcrmektedirler(23,26,27). Bunun sonucunda folik\u00fcl se\u00e7imi (5-10 mm) \u00f6ncesinde bulunan ve daha k\u00fc\u00e7\u00fck (< 2 mm) (preantal) folik\u00fcllerin say\u0131s\u0131 artmaktad\u0131r(21,22,23,24).<\/p>\n\n\n\n

2-<\/mark><\/strong>Polikistik over sendromu olan kad\u0131nlarda folik\u00fcl se\u00e7imi a\u015famas\u0131na (5-10 mm) gelmi\u015f folik\u00fcllerden bir tanesi se\u00e7ilerek daha ileri a\u015famaya ge\u00e7ememektedir (arrested follicles). Bunun sonucunda yumurtlama (ovulation) \u00f6ncesi (preovulatory) olgunlu\u011fa ula\u015fm\u0131\u015f bir folik\u00fcl (dominant) olu\u015fmamaktad\u0131r(28,29,30,31).<\/p>\n\n\n\n

Polikistik over sendromu olan veya olmayan kad\u0131nlarda yumurtlama (ovulation) meydana geldikten yakla\u015f\u0131k 14 g\u00fcn sonra adet kanamas\u0131 (menstruation) ba\u015flamaktad\u0131r. <\/p>\n\n\n\n

Polikistik over sendromu\u2019nda adet d\u00f6ng\u00fcs\u00fcnde ( menstrual cycle) g\u00f6r\u00fclen d\u00fczensizli\u011fin nedeni, se\u00e7ilmi\u015f bir folik\u00fcl\u00fcn geli\u015fip yumurtlama (ovulation) \u00f6ncesi olgun folik\u00fcl (preovulatory) (dominant) a\u015famas\u0131na ula\u015fmas\u0131n\u0131n uzun zaman almas\u0131 (oligo-ovulation) ya da hi\u00e7 ula\u015fmamas\u0131d\u0131r (anovulation) (28,29,30,31).<\/mark><\/strong><\/p>\n\n\n\n

Adet kanamalar\u0131 21 ila 35 g\u00fcn aras\u0131nda de\u011fi\u015fen aral\u0131klarla (eumenorrhea) d\u00fczenli olan kad\u0131nlarda yumurtlama (ovulation) \u00f6ncesi (preovulatory) olgunlu\u011fa ula\u015fm\u0131\u015f bir folik\u00fcl\u00fcn (dominant) olu\u015ftu\u011fu ve bunu takiben yumurtlaman\u0131n (ovulation) meydana geldi\u011fi kabul edilmektedir (10,35,36,37).<\/p>\n\n\n\n

Kad\u0131nlar\u0131n k\u00fc\u00e7\u00fck bir k\u0131sm\u0131nda ise 21 ila 35 g\u00fcn aras\u0131nda (eumenorrhea) d\u00fczenli adet kanamalar\u0131 olmas\u0131na ra\u011fmen yumurtlama (ovulation) \u00f6ncesi olgun folik\u00fcl (preovulatory) (dominant) ve takiben yumurtalama (ovulation) olmamaktad\u0131r (32). 21 ila 35 g\u00fcn aras\u0131nda (eumenorrhea) d\u00fczenli adet kanamalar\u0131 olmas\u0131na ra\u011fmen yumurtlama (ovulation) olmayanlar\u0131n oran\u0131 polikistik over sendromu olan kad\u0131nlarda \u00e7ok daha fazlad\u0131r (2).<\/mark><\/strong><\/p>\n\n\n\n

Erkeklik hormonlar\u0131n\u0131n (testosteron, dihidrotestosteron) miktar\u0131ndaki art\u0131\u015fa (hyperandrogenism) ba\u011fl\u0131 t\u00fcylenme art\u0131\u015f\u0131, sivilce ve sa\u00e7 d\u00f6k\u00fclmesi g\u00f6r\u00fclen kad\u0131nlar\u0131n bir k\u0131sm\u0131nda 21 ila 35 g\u00fcnde bir (eumenorrhea) d\u00fczenli adet kanamalar\u0131 olmas\u0131na ra\u011fmen bunlar\u0131n yakla\u015f\u0131k yar\u0131s\u0131 olgun folik\u00fcl (preovulatory) (dominant) geli\u015fmedi\u011fi i\u00e7in yumurtlama (ovulation) olmadan meydana gelmektedir (2,33,34). <\/mark><\/strong><\/p>\n\n\n\n

Polikistik over sendromu\u2019nda fazla kilolu ve \u015fi\u015fman olan veya normal kilolu fakat bel \u00e7evresi kal\u0131n (erkek tipi ya\u011flanma) olan kad\u0131nlar\u0131n b\u00fcy\u00fck \u00e7o\u011funlu\u011funda ins\u00fclin direnci <\/a>g\u00f6r\u00fclmektedir(139,140,141,142). <\/p>\n\n\n\n

\u0130ns\u00fclin direnci nedeniyle kan dola\u015f\u0131m\u0131nda fazla miktarda bulunan ins\u00fclin hormonu polikistik over sendromu olan kad\u0131nlar\u0131n bir k\u0131sm\u0131nda hem do\u011frudan yumurtal\u0131\u011fa giderek hem de hipofiz bezinde LH (luteinizing hormon) \u00fcretimini artt\u0131rarak olgun folik\u00fcl (preovulatory) (dominant) olu\u015fumunu ve takiben yumurtlamay\u0131 (ovulation) engellemektedir(30,137).<\/mark><\/strong><\/p>\n\n\n\n

Bunun sonucunda adet kanamalar\u0131 35 g\u00fcn ile 3 ay aras\u0131nda de\u011fi\u015fen aral\u0131klarla (oligomenorrhea) veya 3 aydan daha uzun aral\u0131klarla (amenorrhea) olanlarda adet kanamalar\u0131 21 ila 35 g\u00fcnde bir (eumenorrhea) olanlara g\u00f6re ins\u00fclin direnci ve \u015feker hastal\u0131\u011f\u0131 (diabetes mellitus ) daha s\u0131k g\u00f6r\u00fclmektedir(2,143,144,145,146). Adet kanamalar\u0131n\u0131n g\u00f6r\u00fclme aral\u0131klar\u0131 uzad\u0131k\u00e7a ins\u00fclin direncinin \u015fiddeti de artmaktad\u0131r(2,145,146).<\/p>\n\n\n\n

\u00dcreme h\u00fccrelerini (oocyte) i\u00e7inde ta\u015f\u0131yan folik\u00fcllerde (granulosa ve theca h\u00fccreleri) ins\u00fclin hormonu al\u0131c\u0131lar\u0131 (receptors) bulunmaktad\u0131r(147,148,149,150,151,152).<\/p>\n\n\n

\n
\"\"<\/figure>\n<\/div>\n\n\n

Polikistik over sendromu olan kad\u0131nlar\u0131n bir k\u0131sm\u0131nda ins\u00fclin direncine ba\u011fl\u0131 fazla miktarda \u00fcretilen ins\u00fclin (hiperins\u00fclinemi) hormonu ile fazla miktarda \u00fcretilen LH (luteinizing hormon) al\u0131c\u0131lara (receptors) tutunarak folik\u00fcl se\u00e7imi a\u015famas\u0131na (5- 10 mm) gelmi\u015f folik\u00fcllerin yumurtlama (ovulation) \u00f6ncesi (preovulatory) olgun folik\u00fcl (dominant) a\u015famas\u0131na ula\u015fmadan erken d\u00f6nemde b\u00fcy\u00fcmesinin durmas\u0131na (premature arrest) neden olmaktad\u0131r(28,29,138,149,150,151,152).<\/mark><\/strong> Bu nedenle folik\u00fcl se\u00e7imi a\u015famas\u0131na (5-10 mm) gelmi\u015f folik\u00fcllerden bir tanesi se\u00e7ilerek daha ileri a\u015famaya ge\u00e7ememektedir (arrested follicles). Bunun sonucunda da yumurtlama olmamaktad\u0131r (anovulasyon)(28,29,151).<\/mark><\/strong><\/p>\n\n\n\n

Erkeklik hormonlar\u0131 (androgens) yumurtal\u0131klarda en k\u00fc\u00e7\u00fck folik\u00fcllerin (primordial) b\u00fcy\u00fcmesiyle (initiation) olu\u015fan k\u00fc\u00e7\u00fck folik\u00fcllerden (preantral) itibaren yumurtlama \u00f6ncesi olgun folik\u00fcl (preovulatory) a\u015famas\u0131na kadar hatta yumurtlama sonras\u0131nda bile folik\u00fcl\u00fc olu\u015fturan h\u00fccrelerde (granulosa, theca, oocyte) bulunan al\u0131c\u0131lara (receptors) tutunarak etkili olmaktad\u0131r(156,157,159,160,163).<\/p>\n\n\n\n

\u00dcreme h\u00fccrelerini (oocyte) i\u00e7inde ta\u015f\u0131yan dinlenme a\u015famas\u0131nda bulunan en k\u00fc\u00e7\u00fck folik\u00fcllerin (resting follicles) (primordial folik\u00fcl) b\u00fcy\u00fcmeye ba\u015flamas\u0131 ve bu folik\u00fcllerin \u00f6lmeden (atresia) (apoptosis) canl\u0131l\u0131klar\u0131n\u0131 (survival) s\u00fcrd\u00fcrebilmesi i\u00e7in belirli miktarlarda erkeklik hormonlar\u0131na (androgens) ihtiya\u00e7lar\u0131 vard\u0131r(54,154,155).<\/mark><\/strong><\/p>\n\n\n\n

Kad\u0131nlarda 30\u2032 lu ve 40\u2032 l\u0131 ya\u015flardan sonra erkeklik hormonlar\u0131n\u0131n miktarlar\u0131 azalmaktad\u0131r(133,153). Menopoz \u00f6ncesi d\u00f6nemde yumurta say\u0131s\u0131n\u0131n azalmas\u0131 ile birlikte erkeklik hormonlar\u0131 (testosteron, dihidrotestosteron) da azald\u0131\u011f\u0131 i\u00e7in kendili\u011finden (spontaneous) gebe kal\u0131nmas\u0131 zorla\u015fmaktad\u0131r(158). <\/mark><\/strong><\/p>\n\n\n\n

Hatta 30\u2032 lu ve 40\u2032 l\u0131 ya\u015flardan sonra erkeklik hormonlar\u0131n\u0131n azalmas\u0131 \u00e7ocuk iste\u011fi tedavisi nedeniyle yumurta (oocyte) ta\u015f\u0131yan folik\u00fclleri b\u00fcy\u00fctmek i\u00e7in kullan\u0131lan ila\u00e7lar\u0131n etkisini azaltmaktad\u0131r(158,164).<\/p>\n\n\n\n

5- \u03b1 reduktaz (reductase) enzimi yumurtal\u0131klarda yumurtalar\u0131 (oocytes) i\u00e7inde ta\u015f\u0131yan folik\u00fclleri olu\u015fturan h\u00fccrelerde (granulosa, theca) bulunmaktad\u0131r(165,166). 5- \u03b1 reduktaz (reductase) enzimi testosteron hormonunu 10 kat daha g\u00fc\u00e7l\u00fc bir etkiye sahip olan dihidrotestosteron (dhydrotestosterone) hormonuna d\u00f6n\u00fc\u015ft\u00fcrmektedir(167,168,169). Polikistik over sendromu olan kad\u0131nlar\u0131n yumurtal\u0131klar\u0131nda 5- \u03b1 reduktaz (reductase) enziminin etkinli\u011fi (activity) polikistik over sendromu olmayanlardan \u00e7ok daha fazla olup daha fazla miktarda dihidrotestosteron \u00fcretmektedir(166).<\/p>\n\n\n\n

B\u00f6brek \u00fcst\u00fc bezinde fazla miktarda erkeklik hormonu \u00fcretilen kad\u0131nlarda (congenital adrenal hyperplasia) ve kad\u0131ndan erke\u011fe cinsiyet de\u011fi\u015fikli\u011fi (female-to-male transsexulas) amac\u0131yla erkeklik hormonu kullananlarda polikistik over sendromu\u2019nda oldu\u011fu gibi \u00fcreme h\u00fccrelerini (oocyte) i\u00e7inde ta\u015f\u0131yan dinlenme a\u015famas\u0131nda bulunan en k\u00fc\u00e7\u00fck folik\u00fcllerde (resting follicles) (primordial folik\u00fcl) h\u0131zl\u0131 bir b\u00fcy\u00fcme g\u00f6r\u00fclmektedir(161,162). <\/p>\n\n\n\n

Bunun sonucunda folik\u00fcl se\u00e7imi (5-10 mm) \u00f6ncesinde bulunan ve daha k\u00fc\u00e7\u00fck (< 2 mm) (preantal) folik\u00fcllerin say\u0131s\u0131 artmaktad\u0131r. Fakat, folik\u00fcl se\u00e7imi a\u015famas\u0131na (5-10 mm) gelmi\u015f folik\u00fcllerden bir tanesi se\u00e7ilerek daha ileri a\u015famaya ge\u00e7ememektedir (arrested follicles)(161,162).<\/mark><\/strong><\/p>\n\n\n\n

Kad\u0131nlarda erkeklik hormonlar\u0131n\u0131n (androgens) fazlal\u0131\u011f\u0131 (hyperandrogenism) da azl\u0131\u011f\u0131 (hypoandrogenism) da yumurta geli\u015fimini (folliculogenesis) ve yumurtlamay\u0131 (ovulation) engelledi\u011fi i\u00e7in adet d\u00fczensizli\u011fi ile birlikte gebe kalmay\u0131 da zorla\u015ft\u0131rmaktad\u0131r. <\/mark><\/strong><\/p>\n\n\n

\n
\"\"<\/figure>\n<\/div>\n\n\n

Beyinde hipotalamus b\u00f6lgesinde GnRH (Gonadotropin-releasing hormone) salg\u0131layan sinir h\u00fccreleri (neurons) bulunmaktad\u0131r(40,41). GnRH hormonunun belirli aral\u0131klarla art\u0131\u015flar ve azal\u0131\u015flar g\u00f6sterek (pulsatile) salg\u0131lanmas\u0131na ba\u011fl\u0131 olarak hipofiz bezinde LH ve FSH hormonlar\u0131n \u00fcretim s\u0131kl\u0131\u011f\u0131 (frequency) ve miktarlar\u0131 (amplitude) belirlenmektedir(38,39,55).<\/p>\n\n\n\n

Polikistik over sendromu olan kad\u0131nlar\u0131n bir k\u0131sm\u0131nda GnRH hormonu salg\u0131layan jenerat\u00f6r\u00fcn (dinamo) beyinde fazla \u00e7al\u0131\u015fmas\u0131na (hyperactive) ba\u011fl\u0131 olarak GnRH hormonunun belirli aral\u0131klarla (pulsatile) salg\u0131lanma s\u0131kl\u0131\u011f\u0131nda art\u0131\u015f g\u00f6r\u00fclmektedir. <\/mark><\/strong><\/p>\n\n\n\n

Bunun sonucunda polikistik over sendromu olan kad\u0131nlar\u0131n bir k\u0131sm\u0131nda hipofiz bezinde LH hormonunun \u00fcretim s\u0131kl\u0131\u011f\u0131 (frequency), miktar\u0131 (amplitude) ve kan dola\u015f\u0131m\u0131nda bulunan (basal) miktar\u0131 artmaktad\u0131r(38,42,43,44,45,46,47,51,55) Erkeklik hormonlar\u0131n\u0131n yumurtal\u0131kta yap\u0131lmas\u0131n\u0131 sa\u011flayan LH (luteinizing hormon) miktar\u0131n\u0131n artmas\u0131 erkeklik hormonlar\u0131n\u0131n yap\u0131m\u0131n\u0131 artt\u0131rmakla (hiperandrogenism) birlikte yumurtlama \u00f6ncesi olgun folik\u00fcl (dominant) geli\u015fimini ve yumurtlamay\u0131 (ovulasyon) da engellemektedir(27,28,29,30,48,49,50,51,52,53,54,55).<\/mark><\/strong><\/p>\n\n\n\n

1-<\/mark><\/strong>Polikistik over sendromu olan kad\u0131nlar\u0131n bir k\u0131sm\u0131nda GnRH hormonu salg\u0131layan jenerat\u00f6r\u00fcn (dinamo) fazla \u00e7al\u0131\u015fmas\u0131na (hyperactive) neden olan beyinde daha \u00fcst seviyelerde bulunan sinir h\u00fccreleri (neurons) vard\u0131r(56,58,59,63,64,65,66).<\/p>\n\n\n\n

2-<\/mark><\/strong>Bu sinir h\u00fccrelerinden GABA ve Kisspeptin (neurotransmitters) salg\u0131lanmaktad\u0131r. Kisspeptin salg\u0131layan sinir h\u00fccrelerinin bir k\u0131sm\u0131ndan Neurokinin B (NKB) ve Dynorphin (neurotransmitters) de salg\u0131lanmaktad\u0131r(66,67,69,70,71,72,73). <\/p>\n\n\n\n

3-<\/mark><\/strong>Bu maddeler (neurotransmitters) polikistik over sendromu olan kad\u0131nlarda hipofiz bezinde \u00fcretilen LH hormonu miktar\u0131 ile birlikte salg\u0131lanma zaman\u0131n\u0131n s\u0131kl\u0131\u011f\u0131n\u0131 (frequency) da artt\u0131rmaktad\u0131r(56,57,58,59,60,61,62,63,64,65,66,67,68,69,70).<\/p>\n\n\n\n

Polikistik over sendromu olan kad\u0131nlar\u0131n bir k\u0131sm\u0131nda erkeklik hormonlar\u0131n\u0131n (testosteron, dihidrotestosteron) fazla miktarda \u00fcretilmesi (hyperandrogenism) ve ins\u00fclin direncine ba\u011fl\u0131 ins\u00fclin miktar\u0131n\u0131n artmas\u0131 (hyperinsulinemia) beyinde GnRH hormonu salg\u0131layan jenerat\u00f6r\u00fcn (dinamo) fazla \u00e7al\u0131\u015fmas\u0131na (hyperactive) neden olmaktad\u0131r(58,63,74,75). <\/mark><\/strong><\/p>\n\n\n\n

Erkeklik hormonlar\u0131 (testosteron, dihidrotestosteron) ve ins\u00fclin bunu GnRH (Gonadotropin-releasing hormone) salg\u0131layan sinir h\u00fccrelerinden (neurons) daha \u00fcst seviyelerdeki sinir h\u00fccrelerinde \u00fcretilen GABA ve Kisspeptin (neurotransmitters) salg\u0131lanmas\u0131n\u0131 etkileyerek yapmaktad\u0131r(38,63,74,75).<\/p>\n\n\n\n

Beyinde belirli aral\u0131klarla (pulsatile) GnRH hormonu salg\u0131layan jenerat\u00f6r (dinamo) ergenlik (puberte) \u00f6ncesi d\u00f6nemde GnRH hormonunu daha \u00e7ok uyku s\u0131ras\u0131nda salg\u0131lamaktad\u0131r(76,77,78). GnRH hormonu salg\u0131lanmas\u0131nda g\u00fcn i\u00e7inde (day-time) art\u0131\u015f olurken uyku s\u0131ras\u0131nda azalma olmas\u0131yla birlikte ergenlik (puberte) d\u00f6nemi ba\u015flamaktad\u0131r(76,77,78).<\/mark><\/strong><\/p>\n\n\n\n

Yumurtal\u0131klarda yap\u0131lan \u00f6strojen (estrogen) hormonu miktar\u0131n\u0131n artmas\u0131 hipotalamus taraf\u0131ndan GnRH hormonunun belirli aral\u0131klarla (pulsatile) salg\u0131lanmas\u0131 sonucunda hipofiz bezinde \u00fcretilen LH hormonu miktar\u0131nda belirli (surge) bir art\u0131\u015fa (positive feedback) neden olmaktad\u0131r(10,52). LH art\u0131\u015f\u0131n\u0131 (surge) takiben yumurtlama (ovulasyon) olmaktad\u0131r(10,52).<\/mark><\/strong><\/p>\n\n\n

\n
\"\"<\/figure>\n<\/div>\n\n\n

Ergenlik (puberte) d\u00f6neminde hen\u00fcz hipotalamus, hipofiz ve yumurtal\u0131k aras\u0131ndaki ileti\u015fim tam olarak geli\u015fmedi\u011fi (immature) i\u00e7in yumurtlama olmamas\u0131na (anovulasyon) ba\u011fl\u0131 olarak ilk adet kanamas\u0131n\u0131 (menarche) takip eden y\u0131llarda ergenlik d\u00f6neminde bulunan k\u0131zlar\u0131n b\u00fcy\u00fck bir k\u0131sm\u0131nda de\u011fi\u015fik \u015fekillerde adet d\u00fczensizli\u011fi g\u00f6r\u00fclmektedir(6,79,80,81,82,83,84,85,86,111,112,113,114).<\/mark><\/strong><\/p>\n\n\n\n

1-<\/mark><\/strong>Ergenlik d\u00f6neminde (puberte) \u00e7o\u011funlukla 35 g\u00fcnden daha uzun aral\u0131klarla (oligomenorrhea) adet kanamalar\u0131 g\u00f6r\u00fcl\u00fcrken<\/p>\n\n\n\n

2-<\/mark><\/strong>Bir k\u0131sm\u0131nda da 6 aydan daha uzun aral\u0131klarla (secondary amenorrhea) adet kanamalar\u0131 g\u00f6r\u00fclmektedir(85,87,88). <\/p>\n\n\n\n

3-<\/mark><\/strong>Ergenlik d\u00f6neminde bulunan k\u0131zlar\u0131n k\u00fc\u00e7\u00fck bir b\u00f6l\u00fcm\u00fcnde yumurtlama (ovulasyon) olmamas\u0131na ra\u011fmen  adet kanamalar\u0131 21 ila 35 g\u00fcnde bir (eumenorrhea) d\u00fczenli olmaktad\u0131r(89,90,91). <\/p>\n\n\n\n

4-<\/mark><\/strong>Hatta bu k\u0131zlar\u0131n bir b\u00f6l\u00fcm\u00fcnde adet kanamalar\u0131 21 g\u00fcnden daha s\u0131k aral\u0131klarla (polymenorrhea) olmaktad\u0131r(89,90,91,92).<\/p>\n\n\n\n

Ergenlik d\u00f6neminde yumurtlama (ovulasyon) olmamas\u0131 nedeniyle adet kanamalar\u0131 d\u00fczensiz olan k\u0131zlarda ilk adet kanamas\u0131n\u0131 (menarche) takip eden y\u0131llar i\u00e7inde giderek artan s\u0131kl\u0131kta yumurtlaman\u0131n (ovulasyon) oldu\u011fu adet kanamalar\u0131 olmaya ba\u015flamaktad\u0131r(77,82,83). <\/p>\n\n\n\n

\u0130lk adet kanamas\u0131n\u0131 (menarche) takip eden 5 y\u0131l sonunda bu k\u0131zlar\u0131n b\u00fcy\u00fck \u00e7o\u011funlu\u011funda (%80) yumurtlaman\u0131n (ovulasyon) oldu\u011fu d\u00fczenli adet kanamalar\u0131 g\u00f6r\u00fclmektedir(82,83,93). <\/p>\n\n\n\n

\u0130lk adet kanamas\u0131n\u0131 takip eden 5 y\u0131l\u0131n sonunda hala 21 ila 35 g\u00fcnde bir (eumenorrhea) d\u00fczenli adet kanamalar\u0131 g\u00f6r\u00fclmeyenlerde (%20) adet d\u00fczensizli\u011fi ileri ya\u015flara hatta 30 lu 40 l\u0131 ya\u015flara kadar devam etmektedir(77,83,89,93,94,95).<\/p>\n\n\n\n

\u0130lk adet kanamas\u0131n\u0131 (menarche) takip eden 2 y\u0131l sonunda 35 g\u00fcnden daha uzun aral\u0131klarla (oligomenorrhea) veya 6 aydan daha uzun aral\u0131klarla (secondary amenorrhea) adet kanamalar\u0131 g\u00f6r\u00fclen k\u0131zlar\u0131n yar\u0131s\u0131nda polikistik over senromu vard\u0131r(77,83,89,93,94,95). <\/mark><\/strong><\/p>\n\n\n\n

\u0130lk adet kanamas\u0131n\u0131 (menarche) takip eden 2 y\u0131l sonunda adet kanamalar\u0131 35 g\u00fcnden daha uzun aral\u0131klarla (oligomenorrhea) olmaya devam eden bu k\u0131zlar\u0131n b\u00fcy\u00fck bir k\u0131sm\u0131nda LH (luteinizing hormon) ve erkeklik hormonlar\u0131 (testosteron, dihidrotestosteron) kan dola\u015f\u0131m\u0131nda fazla miktarlarda bulunmaktad\u0131r(88,102,103,104,105,106,107,108,109,110).<\/p>\n\n\n\n

\u0130lk adet kanamas\u0131n\u0131 (menarche) takip eden 2 y\u0131l sonunda 35 g\u00fcnden daha uzun aral\u0131klarla (oligomenorrhea) veya 6 aydan daha uzun aral\u0131klarla (secondary amenorrhea) adet kanamalar\u0131 olan k\u0131zlar\u0131n bir k\u0131sm\u0131nda psikolojik kaynakl\u0131 yemek yeme bozukluklar\u0131 (eating disorders) g\u00f6r\u00fclmektedir(115,116,181). <\/mark><\/strong><\/p>\n\n\n\n

Karbonhidrat i\u00e7erikli besinlerin t\u00fcketiminin kesilmesi sonucunda olu\u015fan a\u00e7l\u0131k (starvation) ile birlikte kilo kaybedilmesi (Anorexia Nervosa) 6 aydan daha uzun aral\u0131klarla (secondary amenorrhea) adet kanamalar\u0131 olan k\u0131zlarda daha s\u0131k g\u00f6r\u00fclmektedir(90,91,117,118,170).<\/p>\n\n\n\n

Anorexia Nervosa\u2019 ya ba\u011fl\u0131 olu\u015fan kilo kayb\u0131 nedeniyle beyinde hipotalamus b\u00f6lgesinde bulunan jenerat\u00f6rden (dinamo) GnRH hormonu salg\u0131lanmas\u0131 engellenmektedir (Inhibition). Bunun sonucunda hipofiz bezinden salg\u0131lanan FSH ve LH miktarlar\u0131n\u0131n azalmas\u0131 yumurtal\u0131klarda \u00f6strojen (estrogen) \u00fcretimini azaltarak 6 aydan daha uzun aral\u0131klarla (secondary amenorrhea) adet kanamalar\u0131na (hypothalamic amenorhea) neden olmaktad\u0131r(119,170).<\/p>\n\n\n\n

Polikistik over sendromu nedeniyle kan dola\u015f\u0131m\u0131nda fazla miktarlarda LH (luteinizing hormon) ve ins\u00fclin bulunan 35 g\u00fcnden daha uzun aral\u0131klarla (oligomenorrhea) adet kanamalar\u0131 olan bir k\u0131z a\u015f\u0131r\u0131 kilo kayb\u0131 ya\u015fad\u0131\u011f\u0131 taktirde Polikistik over sendromu\u2019ndan LH (luteinizing hormon) ve ins\u00fclin miktarlar\u0131n\u0131n azald\u0131\u011f\u0131 Anorexia Nervosa\u2019 ya ge\u00e7i\u015f g\u00f6sterebilir. Bu durumda adet kanamalar\u0131 da tamamen kesilebilir (secondary amenorrhea).<\/mark><\/strong><\/p>\n\n\n\n

\"\"<\/figure>\n\n\n\n

A\u015f\u0131r\u0131 yemek yeme ataklar\u0131 sonras\u0131nda kilo al\u0131m\u0131n\u0131 engellemek i\u00e7in kusma y\u00f6ntemi veya ishal yap\u0131c\u0131 ila\u00e7lar\u0131n (laxatives) kullan\u0131lmas\u0131 (Bulimia Nervosa) ya da a\u015f\u0131r\u0131 yemek yemesine ra\u011fmen doyma hissini kaybetti\u011fi ataklar\u0131n olmas\u0131 (Binge eating) \u00e7o\u011funlukla adet kanamalar\u0131 35 g\u00fcn ila 3 ayda bir (oligomenorrhea) olan k\u0131zlarda g\u00f6r\u00fclmektedir(120,121,122,123,124,180,181).<\/mark><\/strong><\/p>\n\n\n\n

A\u00e7l\u0131k (starvation) nedeniyle kilo kaybedilmesi (Anorexia Nervosa) \u015feklinde olan yemek yeme bozuklu\u011fu 6 aydan daha uzun aral\u0131klarla (secondary amenorrhea) adet kanamalar\u0131 olan k\u0131zlarda daha s\u0131k g\u00f6r\u00fcl\u00fcrken, polikistik over sendromu\u2019na ba\u011fl\u0131 erkeklik hormonlar\u0131n\u0131n artmas\u0131 (hyperandrogenism) ile birlikte adet kanamalar\u0131 35 g\u00fcn ila 3 ayda bir (oligomenorrhea) olan k\u0131zlarda yemek yeme bozuklu\u011fu daha \u00e7ok a\u015f\u0131r\u0131 yemek yeme ataklar\u0131 sonras\u0131nda kilo al\u0131m\u0131n\u0131 engellemek i\u00e7in kusma y\u00f6ntemi veya ishal yap\u0131c\u0131 ila\u00e7lar\u0131n (laxatives) kullan\u0131lmas\u0131 (Bulimia Nervosa) ya da a\u015f\u0131r\u0131 yemek yemesine ra\u011fmen doyma hissini kaybetti\u011fi ataklar (Binge eating) \u015feklinde g\u00f6r\u00fclmektedir. A\u015f\u0131r\u0131 yemek yeme iste\u011fi ataklar\u0131 (Food cravings) \u00e7ok be\u011fenilen bir \u00e7e\u015fit yiyecek veya i\u00e7ecek i\u00e7in olmakta olup genellikle bunlar da y\u00fcksek enerji (kalori) i\u00e7eren ya\u011fl\u0131, \u015fekerli ve fast-food besinler olmaktad\u0131r. <\/mark><\/strong><\/p>\n\n\n

\n
\"\"<\/figure>\n<\/div>\n\n\n


Polikistik over sendromu olan k\u0131zlarda ilk adet kanamas\u0131n\u0131n (menarche) g\u00f6r\u00fclme zaman\u0131nda da farkl\u0131l\u0131klar vard\u0131r(4,96,97,98,99)<\/mark><\/strong>;<\/p>\n\n\n\n

1-<\/mark><\/strong>Bu k\u0131zlar\u0131n bir k\u0131sm\u0131nda ilk adet kanamas\u0131 (menarche) \u00f6ncesi folik\u00fcl se\u00e7imi a\u015famas\u0131na (5-10 mm) gelmi\u015f folik\u00fcllerden bir tanesi se\u00e7ilerek daha ileri a\u015famaya ge\u00e7ememektedir (arrested follicles). Bunun sonucunda yumurtlama (ovulation) \u00f6ncesi (preovulatory) olgunlu\u011fa ula\u015fm\u0131\u015f bir folik\u00fcl (dominant) olu\u015fmad\u0131\u011f\u0131 i\u00e7in ilk adet kanamas\u0131 (menarche) gecikerek 16 ya\u015f\u0131ndan sonra olmaktad\u0131r (primary amenorrhea) (28,29,30,31). <\/p>\n\n\n\n

2-<\/mark><\/strong>Polikistik over sendromu olan ve 2500 gram\u2019 dan daha d\u00fc\u015f\u00fck do\u011fum a\u011f\u0131rl\u0131\u011f\u0131 ile do\u011fan k\u0131zlar\u0131n bir k\u0131sm\u0131nda genital b\u00f6lge (pubis) k\u0131llanmas\u0131 8 ya\u015f\u0131ndan \u00f6nce (premature pubarche) ortaya \u00e7\u0131kmaktad\u0131r(100,101). Polikistik over sendromu olan bu k\u0131zlarda da ilk adet kanamas\u0131 (menarche) di\u011fer k\u0131zlara g\u00f6re daha erken ya\u015flarda g\u00f6r\u00fclmektedir(96,98). <\/p>\n\n\n\n

3-<\/mark><\/strong>Polikistik over sendromu olan k\u0131zlar\u0131n fazla kilolu veya \u015fi\u015fman olanlar\u0131nda da ilk adet kanamas\u0131 (menarche) daha erken ya\u015flarda olmaktad\u0131r(4,97,98,99).<\/p>\n\n\n\n

Polikistik over sendromu\u2019ndan kaynaklanan adet d\u00fczensizli\u011finin ergenlik d\u00f6neminde g\u00f6r\u00fclen normal (fizyolojik) kabul edilen adet d\u00fczensizli\u011finden ay\u0131rt edilmesi polikistik over sendromu\u2019nun erken te\u015fhis edilmesini ve ilerlemeden \u00f6nlenmesini sa\u011flamaktad\u0131r.<\/mark><\/strong><\/p>\n\n\n\n

Polikistik over sendromu olan kad\u0131nlar\u0131n bir k\u0131sm\u0131nda se\u00e7ilmi\u015f bir folik\u00fcl\u00fcn geli\u015fip yumurtlama (ovulation) \u00f6ncesi olgun folik\u00fcl (preovulatory) (dominant) a\u015famas\u0131na ula\u015fmas\u0131n\u0131n uzun zaman almas\u0131 (oligo-ovulation) ya da hi\u00e7 ula\u015fmamas\u0131 (anovulation) nedeniyle adet kanamalar\u0131 gecikmekte (oligomenorrhea) ya da hi\u00e7 olmamaktad\u0131r (amenorrhea) (28,29,30,31). <\/p>\n\n\n\n

Bu kad\u0131nlarda ins\u00fclin direnci, bozulmu\u015f \u015feker tolerans\u0131 ve \u015feker hastal\u0131\u011f\u0131 ve bunun sonucunda da metabolik sendrom ergenlik d\u00f6neminden itibaren gen\u00e7 ya\u015flarda (< 40 ya\u015f) polikistik over sendromu olmayan kad\u0131nlara g\u00f6re daha s\u0131k g\u00f6r\u00fclmektedir (125,126,127,128,129,130,131,132).<\/p>\n\n\n\n

Polikistik over sendromu\u2019nun etkisi ve \u015fiddeti 30 lu ya\u015flardan itibaren 40 l\u0131 ya\u015flar\u0131 takiben ve menopoz sonras\u0131 d\u00f6nemde gittik\u00e7e azalmaktad\u0131r.<\/p>\n\n\n\n

Polikistik over sendromu olan kad\u0131nlarda fazla olan erkeklik hormonlar\u0131n\u0131n miktarlar\u0131 (hiperandrogenism) ya\u015f ilerledik\u00e7e 20 li ya\u015flardan itibaren \u00f6zellikle 40 l\u0131 ya\u015flar\u0131 takiben azalmaktad\u0131r(132,133). Fazla say\u0131da olan yumurta (antral folik\u00fcl) say\u0131s\u0131n\u0131n azalmas\u0131na ba\u011fl\u0131 olarak da ya\u015f ilerledik\u00e7e bu kad\u0131nlar\u0131n  adet kanamalar\u0131 daha d\u00fczenli (eumenorrhea) olmaya ba\u015flamakta ve hatta 30 lu ya\u015flar\u0131n ortalar\u0131ndan itibaren bu kad\u0131nlar daha kolay gebe kalabilmektedirler(133,134,135,136,137).<\/p>\n\n\n\n

Tedavi;<\/strong><\/p>\n\n\n\n

Yumurtal\u0131klarda erkeklik hormonu (androgen) \u00fcretimini artt\u0131ran beyinde bulunan GnRH hormonu salg\u0131layan jenerat\u00f6r\u00fcn (dinamo) artm\u0131\u015f olan etkinli\u011finin (activity) azalt\u0131lmas\u0131, erkeklik hormonlar\u0131n\u0131n yumurtal\u0131klarda (ovaries) artm\u0131\u015f olan \u00fcretiminin ve etkinli\u011finin azalt\u0131lmas\u0131 ve erkeklik hormonlar\u0131na ba\u011flanarak onlar\u0131 etkisiz hale getiren Sex hormon Binding Globulin (SHBG) miktar\u0131n\u0131n artt\u0131r\u0131lmas\u0131 sonucunda yumurtay\u0131 i\u00e7inde ta\u015f\u0131yan k\u00fc\u00e7\u00fck keseci\u011fin (folik\u00fcl) b\u00fcy\u00fcmesi (folliculogenesis) ve yumurtlaman\u0131n (ovulation) sa\u011flanmas\u0131 tedavinin temel amac\u0131d\u0131r.<\/p>\n\n\n\n

Polikistik over sendromu\u2019nda adet d\u00fczensizli\u011fi tedavisinde do\u011fum kontrol hap\u0131 kullan\u0131lmas\u0131 do\u011fru de\u011fildir.<\/mark><\/strong><\/p>\n\n\n\n

Do\u011fum kontrol haplar\u0131 polikistik over sendromu\u2019nu tedavi etmemektedir. Bu haplarla meydana gelen adet kanamas\u0131 yumurta geli\u015fimi (folliculogenesis) ve yumurtlama (ovulation) olmadan olu\u015fmaktad\u0131r. Bu nedenle bu kanama ger\u00e7ek bir adet kanamas\u0131 de\u011fildir. Do\u011fum kontrol haplar\u0131 adet d\u00fczensizli\u011fini tedavi etmemekle birlikte bir \u00e7ok yan etkiye de neden olabilmektedir. <\/p>\n\n\n\n

Uzun etkili ve kal\u0131c\u0131 bir tedavi etkinli\u011finin olmamas\u0131na ve bacak damarlar\u0131n\u0131n p\u0131ht\u0131 ile t\u0131kanmas\u0131 (derin ven trombozu) ve ordan kopan p\u0131ht\u0131 par\u00e7as\u0131n\u0131n da akci\u011fer damarlar\u0131n\u0131 t\u0131kamas\u0131 (pulmoner emboli) ve meme kanseri ihtimalini artt\u0131rmas\u0131 gibi bir k\u0131sm\u0131 hayati tehlikeye sahip olan bir \u00e7ok yan etkiye sahip olmas\u0131na ra\u011fmen do\u011fum kontrol haplar\u0131 <\/a>adet d\u00fczensizli\u011fi tedavisinde halen yayg\u0131n olarak kullan\u0131lmaktad\u0131r(171,172,173,174,175,176,177,178).<\/p>\n\n\n\n

Polikistik over sendromu olan kad\u0131nlar\u0131n bir k\u0131sm\u0131nda yumurta geli\u015fimi s\u00fcresinde ve yumurtlama zaman\u0131nda ve bunun sonucunda da adet d\u00fczeninde y\u0131llar i\u00e7inde de\u011fi\u015fiklikler olmaktad\u0131r. Bu durum d\u00fczenli adet g\u00f6rmek i\u00e7in do\u011fum kontrol hap\u0131 kullanan kad\u0131nlar\u0131n  do\u011fum kontrol hap\u0131 kullanmas\u0131na gerek olmadan d\u00fczenli adet g\u00f6rebilecek iken adet d\u00fczensizli\u011finin devam etti\u011fini zannederek gereksiz yere uzun y\u0131llar do\u011fum kontrol hap\u0131 kullanmas\u0131na neden olmaktad\u0131r.<\/mark><\/strong><\/p>\n\n\n\n

Tedavi Y\u00f6ntemleri;<\/strong><\/p>\n\n\n\n

1-<\/mark><\/strong>GnRH hormonu salg\u0131layan jenerat\u00f6r\u00fcn (dinamo) beyinde fazla \u00e7al\u0131\u015fmas\u0131na (hyperactive) ba\u011fl\u0131 olarak GnRH hormonunun belirli aral\u0131klarla (pulsatile) salg\u0131lanma s\u0131kl\u0131\u011f\u0131nda g\u00f6r\u00fclen art\u0131\u015f\u0131n engellenmesi ile hipofiz bezinde LH hormonunun \u00fcretim s\u0131kl\u0131\u011f\u0131 (frequency) ve kan dola\u015f\u0131m\u0131nda bulunan (basal) miktar\u0131n\u0131n azalt\u0131lmas\u0131 bir tedavi se\u00e7ene\u011fidir(38,42,43,44,45,46,47,51,55). Beyinde daha \u00fcst seviyelerde bulunan sinir h\u00fccrelerinden salg\u0131lanan GABA, Kisspeptin, Neurokinin B (NKB) ve Dynorphin (neurotransmitters) GnRH hormonu salg\u0131layan jenerat\u00f6r\u00fcn (dinamo) fazla \u00e7al\u0131\u015fmas\u0131na (hyperactive) neden olmaktad\u0131r(56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73). Bunlar\u0131n GnRH hormonu salg\u0131layan jenerat\u00f6re olan etkilerinin engellenmesi (antagonist) sonucunda erkeklik hormonlar\u0131n\u0131n yumurtal\u0131kta yap\u0131lmas\u0131n\u0131 sa\u011flayan LH (luteinizing hormon) miktar\u0131n\u0131n azalmas\u0131 yumurtal\u0131klarda fazla miktarlarda \u00fcretilen erkeklik hormonlar\u0131n\u0131 (hiperandrogenism) azaltmakla birlikte yumurtlama \u00f6ncesi olgun folik\u00fcl (dominant) geli\u015fimini ve yumurtlamay\u0131 (ovulasyon) da sa\u011flamaktad\u0131r(69,70,71,179).<\/p>\n\n\n\n

2-<\/mark><\/strong>\u0130<\/mark>ns\u00fclin direncine ba\u011fl\u0131 ins\u00fclin miktar\u0131n\u0131n artmas\u0131 (hyperinsulinemia) beyinde GnRH hormonu salg\u0131layan jenerat\u00f6r\u00fcn (dinamo) fazla \u00e7al\u0131\u015fmas\u0131na (hyperactive) neden olmaktad\u0131r(58,63,74,75). \u0130ns\u00fclin direncine ba\u011fl\u0131 fazla miktarda \u00fcretilen ins\u00fclin (hiperins\u00fclinemi) hormonu ile fazla miktarda \u00fcretilen LH (luteinizing hormon) hormonu birlikte (synergistic) al\u0131c\u0131lara (receptors) tutunarak folik\u00fcl se\u00e7imi a\u015famas\u0131na (5- 10 mm) gelmi\u015f folik\u00fcllerin yumurtlama (ovulation) \u00f6ncesi (preovulatory) olgun folik\u00fcl (dominant) a\u015famas\u0131na ula\u015fmadan erken d\u00f6nemde b\u00fcy\u00fcmesinin durmas\u0131na (premature arrest) neden olmaktad\u0131r(28,29,138,149,150,151,152). \u0130ns\u00fclin direncine ba\u011fl\u0131 ins\u00fclin miktar\u0131n\u0131n artmas\u0131 ayn\u0131 zamanda karaci\u011ferde \u00fcretilen SHBG miktar\u0131n\u0131 azaltarak erkeklik hormonlar\u0131n\u0131n serbest dola\u015fan etkin formlar\u0131n\u0131n (serbest testosteron) artmas\u0131na neden olmaktad\u0131r(182,183). Bu nedenlerden dolay\u0131 ins\u00fclin direnci olan kad\u0131nlarda ins\u00fclin duyarl\u0131l\u0131\u011f\u0131n\u0131n ila\u00e7 tedavisi ile artt\u0131r\u0131lmas\u0131na ba\u011fl\u0131 olarak kan dola\u015f\u0131m\u0131nda bulunan ins\u00fclin miktar\u0131n\u0131n azalt\u0131lmas\u0131 bir tedavi se\u00e7ene\u011fidir(202,203).<\/p>\n\n\n\n

3-<\/mark><\/strong>Erkeklik hormonlar\u0131 yumurtal\u0131klarda al\u0131c\u0131lara (androgen receptor) tutunarak folik\u00fcl se\u00e7imi (5-10 mm) \u00f6ncesinde bulunan ve daha k\u00fc\u00e7\u00fck (< 2 mm) (preantal) folik\u00fcllerin say\u0131s\u0131n\u0131 artt\u0131rmaktad\u0131r. Bunu takiben de folik\u00fcl se\u00e7imi a\u015famas\u0131na (5-10 mm) gelmi\u015f folik\u00fcllerden bir tanesinin se\u00e7ilerek daha ileri a\u015famaya ula\u015famamas\u0131na (arrested follicles) neden olmaktad\u0131r(28,29,151). Erkeklik hormonlar\u0131 beyinde GnRH hormonu salg\u0131layan jenerat\u00f6r\u00fcn daha \u00fcst seviyelerinde bulunan al\u0131c\u0131lara tutunarak GnRH hormonu salg\u0131layan jenarat\u00f6r\u00fcn fazla \u00e7al\u0131\u015fmas\u0131na (hyperactivity) neden olmaktad\u0131r(74). Bu nedenlerle erkeklik hormonlar\u0131n\u0131n al\u0131c\u0131lara tutunmas\u0131n\u0131n engellenmesi (androgen receptor antagonist) di\u011fer bir tedavi se\u00e7ene\u011fidir(74,184,185,186,187,188,189,191,192,193,194). Bu ama\u00e7la kullan\u0131lan ila\u00e7lar\u0131n (androgen receptor antagonists) do\u011fum kontrol haplar\u0131 gibi hayati tehlikeye sahip yan etkileri (bacak damarlar\u0131n\u0131n p\u0131ht\u0131 ile t\u0131kanmas\u0131 ve ordan kopan p\u0131ht\u0131 par\u00e7as\u0131n\u0131n da akci\u011fer damarlar\u0131n\u0131 t\u0131kamas\u0131 ve meme kanseri) yoktur(192,195,196,197).<\/p>\n\n\n\n

4-<\/mark><\/strong>Testosteron hormonu  5- \u03b1 reduktaz (reductase) enzimi taraf\u0131ndan yumurtal\u0131klarda 10 kat daha fazla etkiye sahip olan dihidrotestosteron (dhydrotestosterone) hormonuna d\u00f6n\u00fc\u015fmektedir(165,166,167,168,169). 5- \u03b1 reduktaz (reductase) enziminin bu etkisinin engellenmesi (5- \u03b1 reductase inhibitor) de bir tedavi se\u00e7ene\u011fidir(165,166,167,168,169,190). Bu ama\u00e7la kullan\u0131lan ila\u00e7lar\u0131n (5-\u03b1 reductase inhibitors) do\u011fum kontrol haplar\u0131 gibi hayati tehlikeye sahip yan etkileri (bacak damarlar\u0131n\u0131n p\u0131ht\u0131 ile t\u0131kanmas\u0131 ve ordan kopan p\u0131ht\u0131 par\u00e7as\u0131n\u0131n da akci\u011fer damarlar\u0131n\u0131 t\u0131kamas\u0131 ve meme kanseri) yoktur(198).<\/p>\n\n\n

\n
\"\"<\/figure>\n<\/div>\n\n\n

5-<\/mark><\/strong>Polikistik over sendromu\u2019nda miktar\u0131 ve etkinli\u011fi artm\u0131\u015f olan erkeklik hormonlar\u0131n\u0131n (testosteron gibi) b\u00fcy\u00fck bir k\u0131sm\u0131 yumurtal\u0131klar\u0131n d\u0131\u015f k\u0131sm\u0131nda (korteks) \u00fcretilmektedir(205,206,207). Polikistik over sendromu tedavisi i\u00e7in yap\u0131lan ameliyatla yumurtal\u0131klar\u0131n d\u0131\u015f k\u0131sm\u0131na (korteks) elektrik ak\u0131m\u0131 (elektrokoter) veya lazer ile 4 mm \u00e7ap\u0131nda ve 8 mm derinli\u011finde 5-10 adet k\u00fc\u00e7\u00fck delik a\u00e7\u0131larak (laparoskopik ovarian drilling) erkeklik hormonlar\u0131n\u0131n \u00fcretimi ve etkinli\u011fi azalt\u0131l\u0131r(199,200,201). Polikistik over ameliyat\u0131 ins\u00fclin duyarl\u0131l\u0131\u011f\u0131n\u0131n artmas\u0131 sonucunda SHBG miktar\u0131n\u0131 artt\u0131rarak da etki g\u00f6steren bir tedavi se\u00e7ene\u011fidir(199,200,201).<\/p>\n\n\n\n

6-<\/mark><\/strong>D\u00fczenli olarak yap\u0131lan spor (y\u00fcr\u00fcy\u00fc\u015f ve y\u00fczme gibi) kilodan ba\u011f\u0131ms\u0131z olarak yani ki\u015fi fazla kilolu olsa dahi v\u00fccutta bulunan ya\u011f dokusunun yerini kas dokusunun almas\u0131n\u0131 sa\u011flar. Ya\u011f dokusunun azalmas\u0131<\/em><\/a>hem erkeklik hormonlar\u0131n\u0131n \u00fcretimini azaltarak, hem de SHBG miktar\u0131n\u0131 artt\u0131rarak etki g\u00f6steren yard\u0131mc\u0131 bir tedavi se\u00e7ene\u011fidir(204).<\/p>\n\n\n\n

7-<\/mark><\/strong>Fazla miktarda t\u00fcketilen karbonhidratlar proteinlerden farkl\u0131 olarak yumurtal\u0131k ve b\u00f6brek \u00fcst\u00fc bezi gibi erkeklik hormonlar\u0131n\u0131n \u00fcretildi\u011fi b\u00f6lgelerden biri olan ya\u011f dokusu olarak depolanmaktad\u0131r. Bu nedenlerle karbonhidrat miktar\u0131 d\u00fc\u015f\u00fck, buna kar\u015f\u0131l\u0131k protein miktar\u0131 fazla olan besinleri t\u00fcketilmesi hem erkeklik hormonlar\u0131n\u0131n \u00fcretimini d\u00fc\u015f\u00fcrerek, hem de SHBG miktar\u0131n\u0131 artt\u0131rarak etki g\u00f6steren yard\u0131mc\u0131 bir tedavi se\u00e7ene\u011fidir(203,204).<\/p>\n\n\n\n

Yukar\u0131da anlatt\u0131\u011f\u0131m tedavi se\u00e7eneklerinden hangisinin uygulanaca\u011f\u0131 ba\u015fka \u015fikayetlerin (sa\u00e7 d\u00f6k\u00fclmesi, sivilce, t\u00fcylenme art\u0131\u015f\u0131) birlikteli\u011fine ba\u011fl\u0131 olarak ki\u015fiden ki\u015fiye g\u00f6re de\u011fi\u015fmektedir. \u00c7o\u011funlukla birden fazla tedavi se\u00e7ene\u011fi birlikte uygulanmaktad\u0131r.<\/mark><\/strong><\/p>\n\n\n\n

Kaynaklar<\/strong><\/p>\n\n\n\n

1-Clinical and bichemical features of polycystic ovarian disease. Goldzieher JW, Axelrod LR. Fertil Steril. 1963 Nov-Dec;14:631-53.<\/p>\n\n\n\n

2-The severity of menstrual dysfunction as a predictor of insulin resistance in PCOS. Brower M, Brennan K, Pall M, Azziz R. J Clin Endocrinol Metab. 2013 Dec;98(12):E1967-71.<\/p>\n\n\n\n

3-The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report. Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, Janssen OE, Legro RS, Norman RJ,Taylor AE, Witchel SF; Task Force on the Phenotype of the Polycystic Ovary Syndrome of The Androgen Excess and PCOS Society. Fertil Steril. 2009 Feb;91(2):456-88.<\/p>\n\n\n\n

4-Women with polycystic ovary syndrome wedge resected in 1956 to 1965: a long-term follow-up focusing on natural history and circulating hormones. Dahlgren E, Johansson S, Lindstedt G, Knutsson F, Od\u00e9n A, Janson PO, Mattson LA, Crona N, Lundberg PA. Fertil Steril. 1992 Mar;57(3):505-13.<\/p>\n\n\n\n

5-Amenorrhea associated with bilateral polycystic ovaries. Stein IF, Leventhal ML. Am J Obstet Gynecol. 1935, 29(2):181-191.<\/p>\n\n\n\n

6-Variation of the human menstrual cycle through reproductive life. Treloar AE, Boynton RE, Behn BG, Brown BW. Int J Fertil. 1967 Jan-Mar;12(1 Pt 2):77-126.<\/p>\n\n\n\n

7-Polycystic ovary syndrome: the spectrum of the disorder in 1741 patients. Balen AH, Conway GS, Kaltsas G, TechatrasakK, Manning PJ, West C, Jacobs HS. Hum Reprod. 1995 Aug;10(8):2107-11.<\/p>\n\n\n\n

8-Heterogeneity of the polycystic ovary syndrome: clinical, endocrine and ultrasound features in 556 patients. Conway GS, Honour JW, Jacobs HS. Clin Endocrinol (Oxf). 1989 Apr;30(4):459-70.<\/p>\n\n\n\n

9-Androgen excess in women: experience with over 1000 consecutive patients. Azziz R, Sanchez LA, Knochenhauer ES, Moran C, Lazenby J, Stephens KC, Taylor K, Boots LR. J Clin Endocrinol Metab. 2004 Feb;89(2):453-62.<\/p>\n\n\n\n

10-Regulation of ovarian follicular development in primates: facts and hypotheses. Gougeon A . Endocr Rev. 1996 Apr;17(2):121-55.<\/p>\n\n\n\n

11-The microenvironment of the human antral follicle: interrelationships among the steroid levels in antral fluid, the population of granulosa cells, and the status of the oocyte in vivo and in vitro. Mc Natty KP, Smith DM, Makris A, Osathanondh R, Ryan KJ. J Clin Endocrinol Metab. 1979 Dec;49(6):851-60.<\/p>\n\n\n\n

12-Morphological and endocrinological studies on follicular development during the human menstrual cycle. Chikazawa K, Araki S, Tamada T. J Clin Endocrinol Metab. 1986 Feb; 62(2):305-13.<\/p>\n\n\n\n

13-Aspects of ovarian follicle development throughout life. Macklon NS, Fauser BC. Horm Res. 1999;52(4):161-70.<\/p>\n\n\n\n

14-Oocyte apoptosis: like sand through an hourglass. Morita Y, Tilly JL. Dev Biol. 1999 Sep 1;213(1):1-17.<\/p>\n\n\n\n

15-Ovarian follicle atresia: a hormonally controlled apoptotic process. Hsueh AJ, Billig H, Tsafriri A. Endocr Rev. 1994 Dec;15(6):707-24.<\/p>\n\n\n\n

16-Morphometric study of the human neonatal ovary. Forabosco A, Sforza C, De Pol A, Vizzotto L, Marzona L, Ferrario VF. Anat Rec. 1991 Oct;231(2):201-8.<\/p>\n\n\n\n

17-Follicular atresia in the infant human ovary. Himelstein-Braw R, Byskov AG, Peters H, Faber M. J Reprod Fertil. 1976 Jan;46(1):55-9.<\/p>\n\n\n\n

18-Age-related changes of the population of human ovarian follicles: increase in the disappearance rate of non-growing and early-growing follicles in aging women. Gougeon A, Ecochard R, Thalabard JC. Biol Reprod. 1994 Mar;50(3):653-63.<\/p>\n\n\n\n

19-Accelerated disappearance of ovarian follicles in mid-life: implications for forecasting menopause. Faddy MJ, Gosden RG, Gougeon A, Richardson SJ, Nelson JF. Hum Reprod. 1992 Nov;7(10):1342-6.<\/p>\n\n\n\n

20-Biological and clinical importance of ovarian cell death. Tilly JL, Ratts VS. Contemp Ob Gyn. 1996 March:59-86.<\/p>\n\n\n\n

21-Morphology and morphogenesis of the Stein-Leventhal ovary and of so-called \u201chyperthecosis\u201d. Hughesdon PE. Obstet Gynecol Surv. 1982 Feb;37(2):59-77.<\/p>\n\n\n\n

22-Abnormal preantral folliculogenesis in polycystic ovaries is associated with increased granulosa cell division. Stubbs SA, Stark J, Dilworth SM, Franks S, Hardy K. J Clin Endocrinol Metab. 2007 Nov;92(11):4418-26.<\/p>\n\n\n\n

23-Prolonged survival in culture of preantral follicles from polycystic ovaries. Webber LJ, Stubbs SA, Stark J, Margara RA, Trew GH, Lavery SA, Hardy K, Franks S. J Clin Endocrinol Metab. 2007 May;92(5):1975-8.<\/p>\n\n\n\n

24-Formation and early development of follicles in the polycystic ovary. Webber LJ, Stubbs S, Stark J, Trew GH, Margara R, Hardy K, Franks S. Lancet. 2003 Sep 27;362(9389):1017-21.<\/p>\n\n\n\n

25-Interpretation of single progesterone measurement in diagnosis of anovulation and defective luteal phase: observations on analysis of the normal range. Wathen NC, Perry L, Lilford RJ, Chard T. Br Med J (Clin Res Ed). 1984 Jan 7;288(6410):7-9.<\/p>\n\n\n\n

26-Granulosa cells of polycystic ovaries: are they normal or abnormal? Erickson GF, Magoffin DA, Garzo VG, Cheung AP, Chang RJ. Hum Reprod. 1992 Mar;7(3):293-9.<\/p>\n\n\n\n

27-Estradiol production by granulosa cells of normal and polycystic ovaries: relationship to menstrual cycle history and concentrations of gonadotropins and sex steroids in follicular fluid. Mason HD, Willis DS, Beard RW, Winston RM, Margara R, Franks S. J Clin Endocrinol Metab. 1994 Nov;79(5):1355-60.<\/p>\n\n\n\n

28-Premature response to luteinizing hormone of granulosa cells from anovulatory women with polycystic ovary syndrome: relevance to mechanism of anovulation. Willis DS, Watson H, Mason HD, Galea R, Brincat M, Franks S. J Clin Endocrinol Metab. 1998 Nov;83(11):3984-91.<\/p>\n\n\n\n

29-Etiology of anovulation in polycystic ovary syndrome. Franks S, Mason H, White D, Willis D. Steroids. 1998 May-Jun;63(5-6):306-7.<\/p>\n\n\n\n

30-Follicle dynamics and anovulation in polycystic ovary syndrome. Franks S, Stark J, Hardy K. Hum Reprod Update. 2008 Jul-Aug;14(4):367-78.<\/p>\n\n\n\n

31-Nutrition, insulin and polycystic ovary syndrome. Franks S, Robinson S, Willis DS. Rev Reprod. 1996 Jan;1(1):47-53.<\/p>\n\n\n\n

32-Assessment of anovulation in eumenorrheic women: comparison of ovulation detection algorithms. Lynch KE, Mumford SL, Schliep KC, Whitcomb BW, Zarek SM, Pollack AZ, Bertone-Johnson ER, Danaher M, Wactawski-Wende J, Gaskins AJ, Schisterman EF. Fertil Steril. 2004  Aug;102(2):511-518.e2.<\/p>\n\n\n\n

33-Idiopathic hirsutism: an uncommon cause of hirsutism in Alabama. Azziz R, Waggoner WT, Ochoa T, Knochenhauer ES, Boots LR. Fertil Steril. 1998 Aug;70(2):274-8.<\/p>\n\n\n\n

34-Prevalence of idiopathic hirsutism. Carmina E. Eur J Endocrinol. 1998 Oct;139(4):421-3.<\/p>\n\n\n\n

35-Evolution of the diameters of the largest healthy and atretic follicles during the human menstrual cycle. Gougeon A, Lef\u00e8vre B. J Reprod Fertil. 1983 Nov;69(2):497-502.<\/p>\n\n\n\n

36-Follicular development during the luteal phase of the human menstrual cycle. McNatty KP, Hillier SG, van den Boogaard AM, Trimbos-Kemper TC, Reichert LE Jr, van Hall EV. J Clin Endocrinol Metab. 1983 May;56(5):1022-31.<\/p>\n\n\n\n

37-The dominant ovarian follicle. Hodgen GD. Fertil Steril. 1982 Sep;38(3):281-300.<\/p>\n\n\n\n

38-GnRH pulse frequency-dependent differential regulation of LH and FSH gene expression. Thompson IR, Kaiser UB. Mol Cell Endocrinol. 2014 Mar 25;385(1-2):28-35.<\/p>\n\n\n\n

39-The frequency of gonadotropin-releasing-hormone stimulation differentially regulates gonadotropin subunit messenger ribonucleic acid expression. Dalkin AC, Haisenleder DJ, Ortolano GA, Ellis TR, Marshall JC. Endocrinology. 1989 Aug;125(2):917-24.<\/p>\n\n\n\n

40-Pituitary stalk portal blood collection in rhesus monkeys: evidence for pulsatile release of gonadotropin-releasing hormone (GnRH). Carmel PW, Araki S, Ferin M. Endocrinology. 1976 Jul;99(1):243-8.<\/p>\n\n\n\n

41-Frequency and amplitude of gonadotropin-releasing hormone stimulation and gonadotropin secretion in the rhesus monkey. Wildt L, H\u00e4usler A, Marshall G, Hutchison JS, Plant TM, Belchetz PE, Knobil E. Endocrinology. 1981  Aug;109(2):376-85.<\/p>\n\n\n\n

42-Circulating luteinizing hormone pulse frequency in women with polycystic ovary syndrome. Kazer RR, Kessel B, Yen SS. J Clin Endocrinol Metab. 1987 Aug;65(2):233-6.<\/p>\n\n\n\n

43-Opioidergic regulation of LH pulsatility in women with polycystic ovary syndrome. Berga SL, Yen SS. Clin Endocrinol (Oxf). 1989 Feb;30(2):177-84.<\/p>\n\n\n\n

44-Inappropriate secretion of follicle-stimulating hormone and luteinizing hormone in polycystic ovarian disease. Yen SS, Vela P, Rankin J. J Clin Endocrinol Metab. 1970 Apr;30(4):435-42.<\/p>\n\n\n\n

45-Determinants of abnormal gonadotropin secretion in clinically defined women with polycystic ovary syndrome. Taylor AE, McCourt B, Martin KA, Anderson EJ, Adams JM, Schoenfeld D, Hall JE. J Clin Endocrinol Metab. 1997 Jul;82(7):2248-56.<\/p>\n\n\n\n

46-Hyperfunction of the hypothalamic-pituitary axis in women with polycystic ovarian disease: indirect evidence for partial gonadotroph desensitization. Waldstreicher J, Santoro NF, Hall JE, Filicori M, Crowley WF Jr. J Clin Endocrinol Metab. 1988 Jan;66(1):165-72.<\/p>\n\n\n\n

47-Genome-wide association of polycystic ovary syndrome implicates alterations in gonadotropin secretion in European ancestry populations. Hayes MG, Urbanek M, Ehrmann DA, Armstrong LL, Lee JY, Sisk R, Karaderi T, Barber TM, McCarthy MI, Franks S,Lindgren CM, Welt CK, Diamanti-Kandarakis E, Panidis D, Goodarzi MO, Azziz R, Zhang Y, James RG, Olivier M,Kissebah AH; Reproductive Medicine Network, Stener-Victorin E, Legro RS, Dunaif A. Nat Commun. 2015 Aug 18;6:7502.<\/p>\n\n\n\n

48-Increased protein expression of LHCG receptor and 17\u03b1-hydroxylase\/17-20-lyase in human polycystic ovaries. Comim FV, Teerds K, Hardy K, Franks S. Hum Reprod. 2013 Nov;28(11):3086-92.<\/p>\n\n\n\n

49-Developmental programming: rescuing disruptions in preovulatory follicle growth and steroidogenesis from prenatal testosterone disruption. Veiga-Lopez A, Moeller J, Abbott DH, Padmanabhan V. J Ovarian Res. 2016 Jun 29;9(1):39.<\/p>\n\n\n\n

50-Thecal cell sensitivity to luteinizing hormone and insulin in polycystic ovarian syndrome. Cadagan D, Khan R, Amer S. Reprod Biol. 2016 Mar;16(1):53-60.<\/p>\n\n\n\n

51-Metabolic regulation of androgen production by human thecal cells in vitro. Nahum R, Thong KJ, Hillier SG. Hum Reprod. 1995 Jan;10(1):75-81.<\/p>\n\n\n\n

52-Current concepts of the roles of follicle stimulating hormone and luteinizing hormone in folliculogenesis. Hillier SG. Hum Reprod. 1994 Feb;9(2):188-91.<\/p>\n\n\n\n

53-Cellular aspects of pre-ovulatory folliculogenesis in primate ovaries. Hillier SG, Harlow CR, Shaw HJ, Wickings EJ, Dixson AF, Hodges JK. Hum Reprod. 1988 May;3(4):507-11.<\/p>\n\n\n\n

54-Intrafollicular paracrine function of ovarian androgen. Hillier SG. J Steroid Biochem. 1987;27(1-3):351-7.<\/p>\n\n\n\n

55-The origins and sequelae of abnormal neuroendocrine function in polycystic ovary syndrome. Blank SK, McCartney CR, Marshall JC. Hum Reprod Update. 2006 Jul-Aug;12(4):351-61.<\/p>\n\n\n\n

56-Activation of A-type gamma-aminobutyric acid receptors excites gonadotropin-releasing hormone neurons. DeFazio RA, Heger S, Ojeda SR, Moenter SM. Mol Endocrinol. 2002 Dec;16(12):2872-91.<\/p>\n\n\n\n

57-Elevated prenatal anti-M\u00fcllerian hormone reprograms the fetus and induces polycystic ovary syndrome in adulthood. Tata B, Mimouni NEH, Barbotin AL, Malone SA, Loyens A, Pigny P, Dewailly D, Catteau-Jonard S,Sundstr\u00f6m-Poromaa I, Piltonen TT, Dal Bello F, Medana C, Prevot V, Clasadonte J, Giacobini P. Nat Med. 2018 Jun;24(6):834-846.<\/p>\n\n\n\n

58-The neuroendocrine genesis of polycystic ovary syndrome: A role for arcuate nucleus GABA neurons. Moore AM, Campbell RE. J Steroid Biochem Mol Biol. 2016 Jun;160:106-17.<\/p>\n\n\n\n

59-Depolarising and hyperpolarising actions of GABA(A) receptor activation on gonadotrophin-releasing hormone neurones: towards an emerging consensus. Herbison AE, Moenter SM. J Neuroendocrinol. 2011 Jul;23(7):557-69.<\/p>\n\n\n\n

60-Polycystic ovary syndrome: evidence for reduced sensitivity of the gonadotropin-releasing hormone pulse generator to inhibition by estradiol and progesterone. Pastor CL, Griffin-Korf ML, Aloi JA, Evans WS, Marshall JC. J Clin Endocrinol Metab. 1998 Feb;83(2):582-90.<\/p>\n\n\n\n

61-Progesterone inhibition of the hypothalamic gonadotropin-releasing hormone pulse generator: evidence for varied effects in hyperandrogenemic adolescent girls. Chhabra S, McCartney CR, Yoo RY, Eagleson CA, Chang RJ, Marshall JC. J Clin Endocrinol Metab. 2005 May;90(5):2810-5.<\/p>\n\n\n\n

62-Increased cerebrospinal fluid levels of GABA, testosterone and estradiol in women with polycystic ovary syndrome. Kawwass JF, Sanders KM, Loucks TL, Rohan LC, Berga SL. Hum Reprod. 2017 Jul 1;32(7):1450-1456.<\/p>\n\n\n\n

63-Kisspeptins and reproduction: physiological roles and regulatory mechanisms. Pinilla L, Aguilar E, Dieguez C, Millar RP, Tena-Sempere M. Physiol Rev. 2012 Jul;92(3):1235-316.<\/p>\n\n\n\n

64-Kisspeptin signaling in the brain. Oakley AE, Clifton DK, Steiner RA. Endocr Rev. 2009 Oct;30(6):713-43.<\/p>\n\n\n\n

65-Neuroendocrine control by kisspeptins: role in metabolic regulation of fertility. Navarro VM, Tena-Sempere M. Nat Rev Endocrinol. 2011 Sep 13;8(1):40-53.<\/p>\n\n\n\n

66-Minireview: kisspeptin\/neurokinin B\/dynorphin (KNDy) cells of the arcuate nucleus: a central node in the control of gonadotropin-releasing hormone secretion. Lehman MN, Coolen LM, Goodman RL. Endocrinology. 2010 Aug;151(8):3479-89.<\/p>\n\n\n\n

67-Hypertrophy and increased kisspeptin gene expression in the hypothalamic infundibular nucleus of postmenopausal women and ovariectomized monkeys. Rometo AM, Krajewski SJ, Voytko ML, Rance NE. J Clin Endocrinol Metab. 2007 Jul;92(7):2744-50.<\/p>\n\n\n\n

68-The kisspeptin system of the human hypothalamus: sexual dimorphism and relationship with gonadotropin-releasing hormone and neurokinin B neurons. Hrabovszky E, Ciofi P, Vida B, Horvath MC, Keller E, Caraty A, Bloom SR, Ghatei MA, Dhillo WS, Liposits Z, Kallo I. Eur J Neurosci. 2010 Jun;31(11):1984-98.<\/p>\n\n\n\n

69-Neurokinin B Receptor Antagonism in Women With Polycystic Ovary Syndrome: A Randomized, Placebo-Controlled Trial. George JT, Kakkar R, Marshall J, Scott ML, Finkelman RD, Ho TW, Veldhuis J, Skorupskaite K, Anderson RA, McIntosh S, Webber L. J Clin Endocrinol Metab. 2016 Nov;101(11):4313-4321.<\/p>\n\n\n\n

70-Population Pharmacokinetic and Pharmacodynamic Modeling of AZD4901 and Simulation to Support Dose Selection for the Phase 2a Study. Xu H, Li J, Webber L, Kakkar R, Chen Y, Al-Huniti N. J Clin Pharmacol. 2016 Aug;56(8):999-1008.<\/p>\n\n\n\n

71-The NK3 Receptor Antagonist ESN364 Interrupts Pulsatile LH Secretion and Moderates Levels of Ovarian Hormones Throughout the Menstrual Cycle. Fraser GL, Hoveyda HR, Clarke IJ, Ramaswamy S, Plant TM, Rose C, Millar RP. Endocrinology. 2015 Nov;156(11):4214-25.<\/p>\n\n\n\n

72-Investigating the KNDy Hypothesis in Humans by Coadministration of Kisspeptin, Neurokinin B, and Naltrexone in Men. Narayanaswamy S, Prague JK, Jayasena CN, Papadopoulou DA, Mizamtsidi M, Shah AJ, Bassett P, Comninos AN, Abbara A, Bloom SR, Veldhuis JD, Dhillo WS. J Clin Endocrinol Metab. 2016 Sep;101(9):342.<\/p>\n\n\n\n

73-GnRH dysregulation in polycystic ovarian syndrome (PCOS) is a manifestation of an altered neurotransmitter profile. Chaudhari N, Dawalbhakta M, Nampoothiri L. Reprod Biol Endocrinol. 2018 Apr 11;16(1):37.<\/p>\n\n\n\n

74-Polycystic ovarian syndrome: evidence that flutamide restores sensitivity of the gonadotropin-releasing hormone pulse generator to inhibition by estradiol and progesterone.  Eagleson CA, Gingrich MB, Pastor CL, Arora TK, Burt CM, Evans WS, Marshall JC. J Clin Endocrinol Metab. 2000 Nov;85(11):4047-52.<\/p>\n\n\n\n

75-Ontogeny and reversal of brain circuit abnormalities in a preclinical model of PCOS. Silva MS, Prescott M, Campbell RE. JCI Insight. 2018 Apr 5;3(7).<\/p>\n\n\n\n

76-Gonadotrophin releasing hormone pulse generator activity before and during sexual maturation in girls: new insights. Yen SS, Apter D, B\u00fctzow T, Laughlin GA. Hum Reprod. 1993 Nov;8 Suppl 2:66-71.<\/p>\n\n\n\n

77-Serum steroids and pituitary hormones in female puberty: a partly longitudinal study. Apter D. Clin Endocrinol (Oxf).  1980 Feb;12(2):107-20.<\/p>\n\n\n\n

78-Pulsatile secretion of luteinizing hormone in children. Jakachi RI, Kelch RP, Sauder SE, Lloyd JS, Hopwood NJ, Marshall JC. J Clin Endocrinol Metab. 1982 Sep;55(3):453-8.<\/p>\n\n\n\n

79-The absence of positive feedback between estrogen and luteinizing hormone in sexually immature girls. Reiter EO, Kulin HE, Hammond SM. Pediatr Res. 1974 Aug;8(8):740-5.<\/p>\n\n\n\n

80-Adolescent menstrual irregularity. Mansfield MJ, Emans SJ. J Reprod Med. 1984 Jun;29(6):399-410.<\/p>\n\n\n\n

81-Menstrual disorders in adolescence. Slap GB. Best Pract Res Clin Obstet Gynaecol. 2003 Feb;17(1):75-92.<\/p>\n\n\n\n

82-Menstrual irregularities in adolescents: hormonal pattern and ovarian morphology. Venturoli S, Porcu E, Fabbri R, Paradisi R, Ruggeri S, Bolelli G, Orsini LF, Gabbi D, Flamigni C. Horm Res. 1986;24(4):269-79.<\/p>\n\n\n\n

83-Incidence of ovulation in the years after the menarche. Metcalf MG, Skidmore DS, Lowry GF, Mackenzie JA. J Endocrinol. 1983 May;97(2):213-9.<\/p>\n\n\n\n

84-Follicular growth in relation to serum hormonal patterns in adolescent compared with adult menstrual cycles. Apter D, R\u00e4is\u00e4nen I, Yl\u00f6stalo P, Vihko R. Fertil Steril. 1987 Jan;47(1):82-8.<\/p>\n\n\n\n

85-Menstruation in girls and adolescents: using the menstrual cycle as a vital sign. American Academy of Pediatrics Committee on Adolescence; American College of Obstetricians and Gynecologists Committee on Adolescent Health Care, Diaz A, Laufer MR, Breech LL. Pediatrics. 2006 Nov;118(5):2245-50.<\/p>\n\n\n\n

86-Endocrine and metabolic abnormalities in adolescents with a PCOS-like condition: consequences for adult reproduction. Apter D. Trends Endocrinol Metab. 1998 Feb;9(2):58-61.<\/p>\n\n\n\n

87-World Health Organization multicenter study on menstrual and ovulatory patterns in adolescent girls. I. A multicenter cross-sectional study of menarche. World Health Organization Task Force on Adolescent Reproductive Health. J Adolesc Health Care. 1986 Jul;7(4):229-35.<\/p>\n\n\n\n

88-The prognosis for adolescents with menstrual abnormalities. Southam AL, Richart RM. Am J Obstet Gynecol. 1966 Mar 1;94(5):637-45.<\/p>\n\n\n\n

89-Predictive value of menstrual cycle pattern, body mass index, hormone levels and polycystic ovaries at age 15 years for oligo-amenorrhoea at age 18 years. Van Hooff MH, Voorhorst FJ, Kaptein MB, Hirasing RA, Koppenaal C, Schoemaker J. Hum Reprod. 2004 Feb;19(2):383-92.<\/p>\n\n\n\n

90-Prospective follow-up of menstrual disorders in adolescence and prognostic factors. Wiksten-Almstr\u00f6mer M, Hirschberg AL, Hagenfeldt K. Acta Obstet Gynecol Scand. 2008 ;87(11):1162-8.<\/p>\n\n\n\n

91-Menstrual disorders and associated factors among adolescent girls visiting a youth clinic. Wiksten-Almstr\u00f6mer M, Hirschberg AL, Hagenfeldt K. Acta Obstet Gynecol Scand. 2007;86(1):65-72.<\/p>\n\n\n\n

92-Serum sex hormone levels in adolescent girls with polymenorrhoea. Siegberg R, Nilsson CG, Stenman UH, Widholm O. Ann Clin Res.  1987;19(3):183-6.<\/p>\n\n\n\n

93-Endocrine characteristics of adolescent menstrual cycles: impact of early menarche. Vikho R, Apter D. J Steroid Biochem. 1984 Jan;20(1):231-6.<\/p>\n\n\n\n

94-Adult polycystic ovary syndrome begins in childhood. Franks S. Best Pract Res Clin Endocrinol Metab. 2002 Jun;16(2):263-72.<\/p>\n\n\n\n

95-Adolescent polycystic ovary syndrome due to functional ovarian hyperandrogenism persists into adulthood. Rosenfield RL, Ehrmann DA, Littlejohn EE. J Clin Endocrinol Metab. 2015 Apr;100(4):1537-43.<\/p>\n\n\n\n

96-Early puberty-menarche after precocious pubarche: relation to prenatal growth. Ibanez L, Jim\u00e9nez R, de Zegher F. Pediatrics. 2006 Jan;117(1):117-21.<\/p>\n\n\n\n

97-Weight and age at menarche. Stark O, Peckham CS, Moynihan C. Arch Dis Child. 1989 Mar;64(3):383-7.<\/p>\n\n\n\n

98-Environmental and genetic factors influence age at menarche in women with polycystic ovary syndrome. Carroll J, Saxena R, Welt CK. J Pediatr Endocrinol Metab. 2013;25(5-6):459-66.<\/p>\n\n\n\n

99-Body size from birth to adulthood as a predictor of self-reported polycystic ovary syndrome symptoms. Laitinen J, Taponen S, Martikainen H, Pouta A, Millwood I, Hartikainen AL, Ruokonen A, Sovio U, McCarthy MI, Franks S, J\u00e4rvelin MR. Int J Obes Relat Metab Disord. 2003  Jun;27(6):710-5.<\/p>\n\n\n\n

100-Insulin resistance, premature adrenarche, and a risk of the Polycystic Ovary Syndrome (PCOS). Ib\u00e1\u00f1ez L, Potau N, Carrascosa A. Trends Endocrinol Metab. 1998 Feb;9(2):72-7.<\/p>\n\n\n\n

101-Premature adrenarche: etiology, clinical findings, and consequences. Voutilainen R, J\u00e4\u00e4skel\u00e4inen J. J Steroid Biochem Mol Biol. 2015 Jan;145:226-36.<\/p>\n\n\n\n

102-Hormonal pattern of adolescent menstrual cycles. Apter D, Viinikka L, Vihko R. J Clin Endocrinol Metab. 1978 Nov;47(5):944-54.<\/p>\n\n\n\n

103-Polycystic ovary syndrome. Venturoli S, Porcu E, Flamigni C. Curr Opin Pediatr. 1994 Aug;6(4):388-96.<\/p>\n\n\n\n

104-Endocrinologic features of oligomenorrheic adolescent girls. Siegberg R, Nilsson CG, Stenman UH, Widholm O. Fertil Steril. 1986 Nov;46(5):852-7.<\/p>\n\n\n\n

105-Endocrine determinants of fertility: serum androgen concentrations during follow-up of adolescents into the third decade of life. Apter D, Vihko R . J Clin Endocrinol Metab. 1990 Oct;71(4):970-4.<\/p>\n\n\n\n

106-Longitudinal change of sonographic ovarian aspects and endocrine parameters in irregular cycles of adolescence. Venturoli S , Porcu E, Fabbri R, Pluchinotta V, Ruggeri S, Macrelli S, Paradisi R, Flamigni C. Pediatr Res. 1995  Dec;38(6):974-80.<\/p>\n\n\n\n

107-Endocrine features of polycystic ovary syndrome in a random population sample of 14-16 year old adolescents. van Hooff MH, Voorhorst FJ, Kaptein MB, Hirasing RA, Koppenaal C, Schoemaker J. Hum Reprod. 1999 Sep;14(9):2223-9.<\/p>\n\n\n\n

108-Disruption of the joint synchrony of luteinizing hormone, testosterone, and androstenedione secretion in adolescents with polycystic ovarian syndrome. Veldhius JD, Pincus SM, Garcia-Rudaz MC, Ropelato MG, Escobar ME, Barontini M. J Clin Endocrinol Metab. 2001 Jan;86(1):72-9.<\/p>\n\n\n\n

109-Oligomenorrhea in adolescent girls. Emans SJ, Grace E, Goldstein DP.J Pediatr. 1980 Nov;97(5):815-9.<\/p>\n\n\n\n

110-Menstrual disorders in college students. Singh KB. Am J Obstet Gynecol. 1981 Jun 1;140(3):299-302.<\/p>\n\n\n\n

111-Epidemiology of secondary amenorrhea. I. Incidence and prevalence rates. Pettersson F, Fries H, Nillius SJ. Am J Obstet Gynecol. 1973 Sep 1;117(1):80-6.<\/p>\n\n\n\n

112-Prevalence of oligomenorrhea and amenorrhea in a college population. Bachmann GA, Kemmann E. Am J Obstet Gynecol. 1982 Sep 1;144(1):98-102.<\/p>\n\n\n\n

113-Secondary amenorrhoea: prevalence and medical contact\u2013a cross-sectional study from a Danish county. M\u00fcnster K, Helm P, Schmidt L. Br J Obstet Gynaecol. 1992 May;99(5):430-3.<\/p>\n\n\n\n

114-Dysfunctional uterine bleeding and other menstrual problems of secondary school students in Adana, Turkey. Demir SC, Kaday\u0131fc\u0131 TO, Vardar MA, Atay Y. J Pediatr Adolesc Gynecol.2000Nov;13(4):171-5.<\/p>\n\n\n\n

115-Epidemiology of eating disorders: incidence, prevalence and mortality rates. Smink FR, van Hoeken D, Hoek HW. Curr Psychiatry Rep. 2012  Aug;14(4):406-14.<\/p>\n\n\n\n

116-Studies of the epidemiology of bulimia nervosa. Fairburn CG, Beglin SJ. Am J Psychiatry. 1990 Apr;147(4):401-8.<\/p>\n\n\n\n

117-Anorexia nervosa and a bearded female saint. Lacey JH. Br Med J (Clin Res Ed). 1982 Dec 18-25;285(6357):1816-7.<\/p>\n\n\n\n

118-Future recovery of the normal menstrual cycle in adolescent patients with secondary amenorrhea. Morimatsu Y, Matsubara S, Watanabe T, Hashimoto Y, Matsui T, Asada K, Suzuki M. J Obstet Gynaecol Res. 2009Jun;35(3):545-50.<\/p>\n\n\n\n

119-Aetiology, previous menstrual function and patterns of neuro-endocrine disturbance as prognostic indicators in hypothalamic amenorrhoea. Perkins RB, Hall JE, Martin KA. Hum Reprod. 2001 Oct;16(10):2198-205.<\/p>\n\n\n\n

120-Bulimia nervosa: an ominous variant of anorexia nervosa. Russell G. Psychol Med. 1979 Aug;9(3):429-48.<\/p>\n\n\n\n

121-Increased odds of disordered eating in polycystic ovary syndrome: a systematic review and meta-analysis.Lee I, Cooney LG, Saini S, Sammel MD, Allison KC, Dokras A. Eat Weight Disord. 2019 Oct;24(5):787-797.<\/p>\n\n\n\n

122-Increased odds of disordered eating in polycystic ovary syndrome: a systematic review and meta-analysis. Lee I, Cooney LG, Saini S, Sammel MD, Allison KC, Dokras A. Eat Weight Disord. 2019 Oct;24(5):787-797.<\/p>\n\n\n\n

123-Polycystic ovary syndrome and bulimia. McCluskey S, Evans C, Lacey JH, Pearce JM, Jacobs H. Fertil Steril. 1991 Feb;55(2):287-91.<\/p>\n\n\n\n

124-Binge-eating and polycystic ovaries. McCluskey SE, Lacey JH, Pearce JM. Lancet. 1992 Sep 19;340(8821):723.<\/p>\n\n\n\n

125-Relative contributions of oligomenorrhea and hyperandrogenemia to the risk of metabolic syndrome in midlife women. Polotsky AJ, Allshouse A, Crawford SL, Harlow SD, Khalil N, Santoro N, Legro RS. J Clin Endocrinol Metab. 2012 Jun;97(6):E868-77.<\/p>\n\n\n\n

126-Normo- and hyperandrogenic women with polycystic ovary syndrome exhibit an adverse metabolic profile through life. Pinola P, Puukka K, Piltonen TT, Puurunen J, Vanky E, Sundstr\u00f6m-Poromaa I, Stener-Victorin E, Lind\u00e9n Hirschberg A,Ravn P, Skovsager Andersen M, Glintborg D, Mellembakken JR, Ruokonen A, Tapanainen JS, Morin-Papunen LC. Fertil Steril. 2017 Mar;107(3):788-795.<\/p>\n\n\n\n

127-Is the risk for cardiovascular disease increased in all phenotypes of the polycystic ovary syndrome? Daskalopoulos GN, Karkanaki A, Karagiannis A, Mikhailidis DP, Athyros VG. Angiology. 2011 May;62(4):285-90.<\/p>\n\n\n\n

128-Long or highly irregular menstrual cycles as a marker for risk of type 2 diabetes mellitus. Solomon CG, Hu FB, Dunaif A, Rich-Edwards J, Willett WC, Hunter DJ, Colditz GA, Speizer FE, Manson JE. JAMA. 2001 Nov 21;286(19):2421-6.<\/p>\n\n\n\n

129-Metabolic characteristics of women with polycystic ovaries and oligo-amenorrhoea but normal androgen levels: implications for the management of polycystic ovary syndrome. Barber TM, Wass JA, McCarthy MI, Franks S. Clin Endocrinol (Oxf). 2007 Apr;66(4):513-7.<\/p>\n\n\n\n

130-Metabolic cardiovascular disease risk factors in women with self-reported symptoms of oligomenorrhea and\/or hirsutism: Northern Finland Birth Cohort 1966 Study. Taponen S, Martikainen H, J\u00e4rvelin MR, Sovio U, Laitinen J, Pouta A, Hartikainen AL, McCarthy MI, Franks S, Paldanius M,Ruokonen A; Northern Finland Birth Cohort 1966 Study. J Clin Endocrinol Metab. 2004 May;89(5):2114-8.<\/p>\n\n\n\n

131-Hyperandrogenemia is implicated in both the metabolic and reproductive morbidities of polycystic ovary syndrome. Sung YA, Oh JY, Chung H, Lee H. Fertil Steril. 2014 Mar;101(3):840-5.<\/p>\n\n\n\n

132-Phenotypic variation in hyperandrogenic women influences the findings of abnormal metabolic and cardiovascular risk parameters. Carmina E, Chu MC, Longo RA, Rini GB, Lobo RA.J Clin Endocrinol Metab. 2005  May;90(5):2545-9.<\/p>\n\n\n\n

133-Androgen levels in adult females: changes with age, menopause, and oophorectomy. Davison SL, Bell R, Donath S, Montalto JG, Davis SR. J Clin Endocrinol Metab. 2005 Jul;90(7):3847-53.<\/p>\n\n\n\n

134-Women with polycystic ovary syndrome gain regular menstrual cycles when ageing. Elting MW, Korsen TJ, Rekers-Mombarg LT, Schoemaker J. Hum Reprod. 2000 Jan;15(1):24-8.<\/p>\n\n\n\n

135-Serum testosterone levels decrease in middle age in women with the polycystic ovary syndrome. Winters SJ, Talbott E, Guzick DS, Zborowski J, McHugh KP. Fertil Steril. 2000 Apr;73(4):724-9.<\/p>\n\n\n\n

136-Age-related differences in features associated with polycystic ovary syndrome in normogonadotrophic oligo-amenorrhoeic infertile women of reproductive years. Bili H, Laven J, Imani B, Eijkemans MJ, Fauser BC. Eur J Endocrinol. 2001 Dec;145(6):749-55.<\/p>\n\n\n\n

137-Long-term follow-up of patients with polycystic ovary syndrome: reproductive outcome and ovarian reserve. Hudecova M, Holte J, Olovsson M, Sundstr\u00f6m Poromaa I. Hum Reprod. 2009 May;24(5):1176-83.<\/p>\n\n\n\n

138-Modulation by insulin of follicle-stimulating hormone and luteinizing hormone actions in human granulosa cells of normal and polycystic ovaries. Willis D, Mason H, Gilling- Smith C, Franks S. J Clin Endocrinol Metab. 1996 Jan;81(1):302-9.<\/p>\n\n\n\n

139-Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome. Dunaif A, Segal KR, Futterweit W, Dobrjansky A. Diabetes. 1989 Sep;38(9):1165-74.<\/p>\n\n\n\n

140-Prediction models for insulin resistance in the polycystic ovary syndrome. Gennarelli G, Holte J, Berglund L, Berne C, Massobrio M, Lithell H. Hum Reprod. 2000 Oct;15(10):2098-102.<\/p>\n\n\n\n

141-Use of fasting blood to assess the prevalence of insulin resistance in women with polycystic ovary syndrome. Carmina E, Lobo RA. Fertil Steril. 2004  Sep;82(3):661-5.<\/p>\n\n\n\n

142-Prevalence of insulin resistance in the polycystic ovary syndrome using the homeostasis model assessment. DeUgarte CM, Bartolucci AA, Azziz R. Fertil Steril. 2005 May;83(5):1454-60.<\/p>\n\n\n\n

143-The relationship of insulin insensitivity to menstrual pattern in women with hyperandrogenism and polycystic ovaries. Robinson S, Kiddy D, Gelding SV, Willis D, Niththyananthan R, Bush A, Johnston DG, Franks S. Clin Endocrinol (Oxf). 1993 Sep;39(3):351-5.<\/p>\n\n\n\n

144-Characterization of groups of hyperandrogenic women with acanthosis nigricans, impaired glucose tolerance, and\/or hyperinsulinemia. Dunaif A, Graf M, Mandeli J, Laumas V, Dobrjansky A. J Clin Endocrinol Metab. 1987 Sep;65(3):499-507.<\/p>\n\n\n\n

145-Menstrual Cycle Irregularity and Metabolic Disorders: A Population-Based Prospective Study. Rostami Dovom M, Ramezani Tehrani F, Djalalinia S, Cheraghi L, Behboudi Gandavani S, Azizi F. PLoS One. 2016 Dec 16;11(12):e0168402.<\/p>\n\n\n\n

146-Long or highly irregular menstrual cycles as a marker for risk of type 2 diabetes mellitus. Solomon CG, Hu FB, Dunaif A, Rich-Edwards J, Willett WC, Hunter DJ, Colditz GA, Speizer FE, Manson JE. JAMA. 2001 Nov 21;286(19):2421-6.<\/p>\n\n\n\n

147-Specific insulin binding sites in human ovary. Poretsky L, Smith D, Seibel M, Pazianos A, Moses AC, Flier JS. J Clin Endocrinol Metab. 1984 Oct;59(4):809-11.<\/p>\n\n\n\n

148-Distribution and characterization of insulin and insulin-like growth factor I receptors in normal human ovary. Poretsky L, Grigorescu F, Seibel M, Moses AC, Flier JS. J Clin Endocrinol Metab. 1985 Oct;61(4):728-34.<\/p>\n\n\n\n

149-Altered expression of insulin and insulin-like growth factor-I receptors in follicular and stromal compartments of polycystic ovaries. Samoto T, Maruo T, Matsuo H, Katayama K, Barnea ER, Mochizuki M. Endocr J. 1993 Aug;40(4):413-24.<\/p>\n\n\n\n

150-Insulin receptor expression in follicular and stromal compartments of the human ovary over the course of follicular growth, regression and atresia. Samoto T, Maruo T, Ladines-Llave CA, Matsuo H, Deguchi J, Barnea ER, Mochizuki M. Endocr J. 1993 Dec;40(6):715-26.<\/p>\n\n\n\n

151-Insulin action in human granulosa cells from normal and polycystic ovaries is mediated by the insulin receptor and not the type-I insulin-like growth factor receptor. Willis D, Franks S. J Clin Endocrinol Metab. 1995 Dec;80(12):3788-90.<\/p>\n\n\n\n

152-Insulin preincubation enhances insulin-like growth factor-II (IGF-II) action on steroidogenesis in human granulosa cells. Mason HD, Willis DS, Holly JM, Franks S. J Clin Endocrinol Metab. 1994 May;78(5):126.<\/p>\n\n\n\n

153-Twenty-four-hour mean plasma testosterone concentration declines with age in normal premenopausal women. Zumoff B, Strain GW, Miller LK, Rosner W. J Clin Endocrinol Metab. 1995 Apr;80(4):1429-30.<\/p>\n\n\n\n

154-Evidence that granulosa cell aromatase induction\/activation by follicle-stimulating hormone is an androgen receptor-regulated process in-vitro. Hillier SG, De Zwart FA. Endocrinology. 1981 Oct;109(4):1303-5.<\/p>\n\n\n\n

155-Role of androgens in follicle maturation and atresia. Hillier SG, Tetsuka M. Baillieres Clin Obstet Gynaecol. 1997 Jun;11(2):249-60.<\/p>\n\n\n\n

156-Stage-specific expression of androgen receptor, follicle-stimulating hormone receptor, and anti-M\u00fcllerian hormone type II receptor in single, isolated, human preantral follicles: relevance to polycystic ovaries. Rice S, Ojha K, Whitehead S, Mason H. J Clin Endocrinol Metab. 2007 Mar;92(3):1034-40.<\/p>\n\n\n\n

157-In human granulosa cells from small antral follicles, androgen receptor mRNA and androgen levels in follicular fluid correlate with FSH receptor mRNA. Nielsen ME, Rasmussen IA, Kristensen SG, Christensen ST, M\u00f8llg\u00e5rd K, Wreford Andersen E, Byskov AG, Andersen C. Mol Hum Reprod. 2011 Jan;17(1):63-70.<\/p>\n\n\n\n

158-Androgens regulate ovarian follicular development by increasing follicle stimulating hormone receptor and microRNA-125b expression. Sen A, Prizant H, Light A, Biswas A, Hayes E, Lee HJ, Barad D, Gleicher N, Hammes SR. Proc Natl Acad Sci U S A. 2014 Feb 25;111(8):3008-13.<\/p>\n\n\n\n

159-Cloning of human androgen receptor complementary DNA and localization to the X chromosome. Lubahn DB, Joseph DR, Sullivan PM, Willard HF, French FS, Wilson EM. Science. 1988 Apr 15;240(4850):327-30.<\/p>\n\n\n\n

160-Androgen receptor defects: historical, clinical, and molecular perspectives. Quigley CA, De Bellis A, Marschke KB, el-Awady MK, Wilson EM, French FS. Endocr Rev. 1995 Jun;16(3):271-321.<\/p>\n\n\n\n

161-The prevalence of polycystic ovaries in patients with congenital adrenal hyperplasia and their close relatives. Hague WM, Adams J, Rodda C, Brook CG, de Bruyn R, Grant DB, Jacobs HS. Clin Endocrinol (Oxf). 1990 Oct;33(4):501-10.<\/p>\n\n\n\n

162-Polycystic ovaries in female-to-male transsexuals. Pache TD, Fauser BC. Clin Endocrinol (Oxf). 1993 Dec;39(6):702-3.<\/p>\n\n\n\n

163-Immunohistochemical localization of androgen receptor in the human ovary throughout the menstrual cycle in relation to oestrogen and progesterone receptor expression. Horie K, Takakura K, Fujiwara H, Suginami H, Liao S, Mori T. Hum Reprod. 1992 Feb;7(2):184-90.<\/p>\n\n\n\n

164-Androgen priming using aromatase inhibitor and hCG during early-follicular-phase GnRH antagonist down-regulation in modified antagonist protocols. Lossl K, Andersen AN, Loft A, Freiesleben NL, Bangsb\u00f8ll S, Andersen CY. Hum Reprod. 2006 Oct;21(10):2593-600.<\/p>\n\n\n\n

165-5alpha-reductase 1 and 2 expression and activity in human ovarian follicles, stroma and corpus luteum as compared to neonatal foreskin. Haning RV, Jr, Tantravahi U, Zhao Q, Hackett RJ, Canick JA. J Steroid Biochem Mol Biol. 1996 Oct;59(2):199-204.<\/p>\n\n\n\n

166-5alpha-reductase activity in women with polycystic ovary syndrome. Jakimiuk AJ, Weitsman SR, Magoffin DA. J Clin Endocrinol Metab. 1999 Jul;84(7):2414-8.<\/p>\n\n\n\n

167-Sexual hormones in human skin. Zouboulis CC, Chen WC, Thornton MJ, Qin K, Rosenfield R. Horm Metab Res. 2007 Feb;39(2):85-95.<\/p>\n\n\n\n

168-Dihydrotestosterone is a peripheral paracrine hormone. Horton R. J Androl. 1992 Jan-Feb;13(1):23-7.<\/p>\n\n\n\n

169-Relative binding affinity of anabolic-androgenic steroids: comparison of the binding to the androgen receptors in skeletal muscle and in prostate, as well as to sex hormone-binding globulin. Saartok T, Dahlberg E, Gustafsson JA. Endocrinology. 1984 Jun;114(6):2100-6.<\/p>\n\n\n\n

170-How possible is the prevention of polycystic ovary syndrome development in adolescent patients with early onset of hyperandrogenism. Apter D. J Endocrinol Invest. 1998 Oct;21(9):613-7.<\/p>\n\n\n\n

171-Risk of venous thromboembolism in women with polycystic ovary syndrome: a population-based matched cohort analysis. Bird ST, Hartzema AG, Brophy JM, Etminan M, Delaney JA. CMAJ. 2013 Feb 5;185(2):E115-20.<\/p>\n\n\n\n

172-Combined hormonal contraception and the risk of venous thromboembolism: a guideline. Practice Committee of the American Society for Reproductive Medicine. Fertil Steril. 2017 Jan;107(1):43-51.<\/p>\n\n\n\n

173-Different combined oral contraceptives and the risk of venous thrombosis:systematic review and network meta-analysis. Stegeman BH, de Bastos M, Rosendaal FR, van Hylckama Vlieg A, Helmerhorst FM, Stijnen T, Dekkers OM. BMJ.  2013 Sep 12;347:f5298.<\/p>\n\n\n\n

174-Pills-related severe adverse events: A case report in Taiwan. Chen CH, Chin HY et al. Taiwan J Obstet Gynecol . 2016 Aug;55(4):588-90.<\/p>\n\n\n\n

175-Oral contraceptives and breast cancer risk among younger women. Brinton LA, Daling JR, Liff JM et al. J Nath Cancer Inst. 1995 Jun 7;87(11):827-35.<\/p>\n\n\n\n

176-Contemporary Hormonal Contraception and the Risk of Breast Cancer. M\u00f8rch LS, Skovlund CW, Hannaford PC, Iversen L, Fielding S, Lidegaard \u00d8. N Engl J Med. 2017 Dec 7;377(23):2228-2239.<\/p>\n\n\n\n

177-Breast cancer and hormonal contraceptives: collaborative reanalysis of individual data on 53 297 women with breast cancer and 100 239 women without breast cancer from 54 epidemiological studies.Collaborative Group on Hormonal Factors in Breast Cancer.Lancet. 1996 Jun 22;347(9017):1713-27.<\/p>\n\n\n\n

178-Breast cancer among young U.S. women in relation to oral contraceptive use. White E, Malone KE, Weiss NS, Daling JR. J Natl Cancer Inst. 1994 Apr 6;86(7):505-14.<\/p>\n\n\n\n

179-Optimization of Novel Antagonists to the Neurokinin-3 Receptor for the Treatment of Sex-Hormone Disorders (Part II). Hoveyda HR, Fraser GL, Dutheuil G, El Bousmaqui M, Korac J, Lenoir F, Lapin A, No\u00ebl S. ACS Med Chem Lett. 2015 May 19;6(7):736-40.<\/p>\n\n\n\n

180-Development and validation of the food-craving inventory. White MA, Whisenhunt BL, Williamson DA, Greenway FL, Netemeyer RG. Obes Res. 2002 Feb;10(2):107-14.<\/p>\n\n\n\n

181-Binge eating behaviours and food cravings in women with Polycystic Ovary Syndrome. Jeanes YM, Reeves S, Gibson EL, Piggott C, May VA, Hart KH. Appetite. 2017  Feb 1;109:24-32.<\/p>\n\n\n\n

182-Clinical review: Insulin sensitizers for the treatment of hirsutism: a systematic review and metaanalyses of randomized controlled trials. Cosma M, Swiglo BA, Flynn DN, Kurtz DM, Labella ML, Mullan RJ, Elamin MB, Erwin PJ, Montori VM. J Clin Endocrinol Metab. 2008 Apr;93(4):1135-42.<\/p>\n\n\n\n

183- Treatment Options for Hirsutism: A Systematic Review and Network Meta- Analysis . Barrionuevo P, Nabhan M, Altayar O, Wang Z, Erwin PJ, Asi N, Martin KA, Murad MH. J Clin Endocrinol Metab. 2018 Apr 1;103(4):1258-1264.<\/p>\n\n\n\n

184-The endocrine effects of spironolactone used as an antiandrogen. Young RL, Goldzieher JW, Elkind-Hirsch K. Fertil Steril. 1987 Aug;48(2):223-8.<\/p>\n\n\n\n

185-A systematic review of commonly used medical treatments for hirsutism in women. Koulouri O, Conway GS. Clin Endocrinol (Oxf). 2008 May;68(5):800-5.<\/p>\n\n\n\n

186-Comparison of spironolactone, flutamide, and finasteride efficacy in the treatment of hirsutism: a randomized, double blind, placebo-controlled trial. Moghetti P, Tosi F, Tosti A, Negri C, Misciali C, Perrone F, Caputo M, Muggeo M, Castello R. J Clin Endocrinol Metab. 2000 Jan;85(1):89-94.<\/p>\n\n\n\n

187-Hormonal effects of flutamide in young women with polycystic ovary syndrome. De Leo V, Lanzetta D, D\u2019Antona D, la Marca A, Morgante G. J Clin Endocrinol Metab. 1998 Jan;83(1):99-102.<\/p>\n\n\n\n

188-Ovulatory effects of flutamide in the polycystic ovary syndrome. Paradisi, Fabbri R, Battaglia C, Venturoli S. Gynecol Endocrinol. 2013 Apr;29(4):391-5.<\/p>\n\n\n\n

189-Treatment with flutamide, metformin, and their combination added to a hypocaloric diet in overweight-obese women with polycystic ovary syndrome: a randomized, 12-month, placebo-controlled study. Gambineri A, Patton L, Vaccina A, Cacciari M, Morselli-Labate AM, Cavazza C, Pagotto U, Pasquali R. J Clin Endocrinol Metab. 2006 Oct;91(10):3970-80.<\/p>\n\n\n\n

190-Effect of finasteride on ovulation induction in nonresponder (hyperandrogenic) polycystic ovary syndrome (PCOS) women. Tartagni M, Cicinelli E, De Pergola G, Lavopa C, Di Naro E, De Salvia MA, Loverro G. Fertil Steril. 2010 Jun;94(1):247-9.<\/p>\n\n\n\n

191-Combined Oral Contraception and Bicalutamide in Polycystic Ovary Syndrome and Severe Hirsutism: A Double-Blind Randomized Controlled Trial. Moretti C, Guccione L, Di Giacinto P, Simonelli I, Exacoustos C, Toscano V, Motta C, De Leo V, Petraglia F, Lenzi A.J Clin Endocrinol Metab. 2018 Mar 1;103(3):824-838.<\/p>\n\n\n\n

192-An overview of animal toxicology studies with bicalutamide (J Toxicol Sci. 1997  May;22(2):75-88.ICI 176,334). Iswaran TJ, Imai M, Betton GR, Siddall RA. J Toxicol Sci. 1997 May;22(2):75-88.<\/p>\n\n\n\n

193-Oral bicalutamide for female pattern hair loss: A pilot study. Fernandez -Nieto D, Saceda-Corralo D, Rodrigues-Barata R, Hermosa-Gelbard A, Moreno-Arrones O, Jimenez-Cauhe J, Ortega-Quijano D, Vano-Galvan S. Dermatol Ther. 2019 Nov;32(6):e13096.<\/p>\n\n\n\n

194-Low-dose flutamide-metformin therapy for hyperinsulinemic
hyperandrogenism in non-obese adolescents and women. Lourdes Ib\u00e1\u00f1ez, and Francis de Zegher. Human Reproduction Update. 2006 Vol.12, No.3 pp. 243\u2013252.<\/p>\n\n\n\n

195-Spironolactone and risk of incident breast cancer in women older than 55 years: retrospective, matched cohort study. Mackenzie IS, Macdonald TM, Thompson A, Morant S, Wei L. BMJ. 2012 Jul 13;345:e4447.<\/p>\n\n\n\n

196-Spironolactone use and risk of incident cancers: a retrospective, matched cohort study. Mackenzie IS, Morant SV, Wei L, Thompson AM, MacDonald TM. Br J Clin Pharmacol. 2017 Mar;83(3):653-663.<\/p>\n\n\n\n

197-Spironolactone use and the risk of breast and gynecologic cancers. Biggar RJ, Andersen EW, Wohlfahrt J, Melbye M. Cancer Epidemiol. 2013 Dec;37(6):870-5<\/p>\n\n\n\n

198-Adverse Effects and Safety of 5-alpha Reductase Inhibitors (Finasteride, Dutasteride): A Systematic Review. Hirshburg JM, Kelsey PA, Therrien CA, Gavino AC, Reichenberg JS. J Clin Aesthet Dermatol. 2016 Jul;9(7):56-62.<\/p>\n\n\n\n

199-Long term follow-up of  patients with polycystic ovarian syndrome after laparoscopic ovarian drilling: clinical outcome. Amer SA, Gopalan V, Li TC, Ledger WL, Cooke ID. Hum Reprod. 2002 Aug;17(8):2035-42.<\/p>\n\n\n\n

200-Effects of laparoscopic ovarian drilling on adrenal steroids in polycystic ovary syndrome patients with and without hyperinsulinemia. Saleh A, Morris D, Tan SL, Tulandi T. Fertil Steril. 2001 Mar;75(3):501-4.<\/p>\n\n\n\n

201-Success of laparoscopic ovarian wedge resection is related to obesity, lipid profile, and insulin levels. Duleba AJ, Banaszewska B, Spaczynski RZ, Pawelczyk L. Fertil Steril. 2003 Apr;79(4):1008-14.<\/p>\n\n\n\n

202-Is Metformin the Answer for Distressed Females with Menstrual Irregularities?Tejpal C, Poudel I, Jahan N. Cureus. 2019 Aug 22;11(8):e5460.<\/p>\n\n\n\n

203-Metformin and lifestyle modification in polycystic ovary syndrome: systematic review and meta-analysis.Naderpoor N, Shorakae S, de Courten B, Misso ML, Moran LJ, Teede HJ. Hum Reprod Update. 2015 Sep-Oct;21(5):560-74.<\/p>\n\n\n\n

204-Lifestyle changes in women with polycystic ovary syndrome. Moran LJ, Hutchison SK, Norman RJ, Teede HJ. Cochrane Database Syst Rev. 2011 Jul 6;(7):CD0075.<\/p>\n\n\n\n

205-Functional integrity of granulosa cells from polycystic ovaries. Almahbobi  G, Anderiesz C, Hutchinson P, McFarlane JR, Wood C, Trounson AO. Clin Endocrinol (Oxf).<\/a> 1996 May;44(5):571-80.<\/p>\n\n\n\n

206-Hypersecretion of androstenedione by isolated thecal cells from polycystic ovaries. Gilling-Smith C, Willis DS, Beard RW, Franks S. J Clin Endocrinol Metab. 1994 Oct;79(4):1158-65.<\/p>\n\n\n\n

207-Evidence for a primary abnormality of thecal cell steroidogenesis in the polycystic ovary syndrome. Gilling-Smith C, Story H, Rogers V, Franks S. Clin Endocrinol (Oxf). 1997 Jul;47(1):93-9.<\/p>\n\n\n\n

<\/p>\n\n\n\n

<\/p>\n\n\n\n

<\/p>\n\n\n\n

<\/p>\n\n\n\n

<\/p>\n\n\n\n

<\/p>\n","protected":false},"excerpt":{"rendered":"

Bir adet kanamas\u0131n\u0131n ba\u015flang\u0131c\u0131ndan itibaren takip eden adet kanamas\u0131n\u0131n ilk g\u00fcn\u00fcne kadar ge\u00e7en s\u00fcre bir adet d\u00f6ng\u00fcs\u00fcd\u00fcr (menstrual cycle). Polikistik over sendromu olan kad\u0131nlar\u0131n b\u00fcy\u00fck bir k\u0131sm\u0131n\u0131n adet d\u00f6ng\u00fclerinde d\u00fczensizlik vard\u0131r(1,4,5,7,8,9). Polikistik over sendromu\u2019nda adet d\u00fczensizli\u011fi de\u011fi\u015fik \u015fekillerde ortaya \u00e7\u0131kmaktad\u0131r; 1- Bu kad\u0131nlarda \u00e7o\u011funlukla 35 g\u00fcn ile 3 ay aras\u0131nda de\u011fi\u015fen aral\u0131klarla (oligomenorrhea) adet kanamalar\u0131 (2,4,7,8,9). […]<\/p>\n","protected":false},"author":1,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"class_list":["post-6432","page","type-page","status-publish","hentry"],"_links":{"self":[{"href":"https:\/\/polikistikover.net\/yeni\/wp-json\/wp\/v2\/pages\/6432","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/polikistikover.net\/yeni\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/polikistikover.net\/yeni\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/polikistikover.net\/yeni\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/polikistikover.net\/yeni\/wp-json\/wp\/v2\/comments?post=6432"}],"version-history":[{"count":17,"href":"https:\/\/polikistikover.net\/yeni\/wp-json\/wp\/v2\/pages\/6432\/revisions"}],"predecessor-version":[{"id":12841,"href":"https:\/\/polikistikover.net\/yeni\/wp-json\/wp\/v2\/pages\/6432\/revisions\/12841"}],"wp:attachment":[{"href":"https:\/\/polikistikover.net\/yeni\/wp-json\/wp\/v2\/media?parent=6432"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}